Apparatus and methods for filling a drug eluting medical device via capillary action

ABSTRACT

Methods and apparatus are disclosed for filling a therapeutic substance or drug within a hollow wire that forms a stent. The stent is placed within a chamber housing a fluid drug formulation. During filling, the chamber is maintained at or near the vapor-liquid equilibrium of the solvent of the fluid drug formulation. To fill the stent, a portion of the stent is placed into contact with the fluid drug formulation until a lumenal space defined by the hollow wire is filled with the fluid drug formulation via capillary action. After filling is complete, the stent is retracted such that the stent is no longer in contact with the fluid drug formulation. The solvent vapor pressure within the chamber is reduced to evaporate a solvent of the fluid drug formulation. A wicking means may control transfer of the fluid drug formulation into the stent.

RELATED APPLICATIONS

This application is a Continuation of and claims the benefit of U.S.patent application Ser. No. 13/457,418 filed Apr. 26, 2012, now allowed.The disclosures of which are herein incorporated by reference in theirentirety.

FIELD OF THE INVENTION

The invention relates generally to implantable medical devices thatrelease a therapeutic substance or drug, and more particularly toapparatuses and methods of loading or filling such medical devices withthe therapeutic substance or drug.

BACKGROUND OF THE INVENTION

Drug-eluting implantable medical devices are useful for their ability toprovide structural support while medically treating the area in whichthey are implanted. For example, drug-eluting stents have been used toprevent restenosis in coronary arteries. Drug-eluting stents mayadminister therapeutic agents such as anti-inflammatory compounds thatblock local invasion/activation of monocytes, thus preventing thesecretion of growth factors that may trigger VSMC proliferation andmigration. Other potentially anti-restenotic compounds includeantiproliferative agents, such as chemotherapeutics, which includesirolimus and paclitaxel. Other classes of drugs such asanti-thrombotics, anti-oxidants, platelet aggregation inhibitors andcytostatic agents have also been suggested for anti-restenotic use.

Drug-eluting medical devices may be coated with a polymeric materialwhich, in turn, is impregnated with a drug or a combination of drugs.Once the medical device is implanted at a target location, the drug isreleased from the polymer for treatment of the local tissues. The drugis released by a process of diffusion through a polymer layer of abiostable polymer, and/or as the polymer material degrades when thepolymer layer is of a biodegradable polymer.

Drug impregnated polymer coatings are limited in the quantity of thedrug to be delivered by the amount of a drug that the polymer coatingcan carry and the size of the medical device. As well, controlling therate of elution using polymer coatings is difficult.

Accordingly, drug-eluting medical devices that enable increasedquantities of a drug to be delivered by the medical device, and allowfor improved control of the elution rate of the drug, and improvedmethods of forming such medical devices are needed. Co-pending U.S.Patent Application Publication No. 2011/0008405, filed Jul. 9, 2009,U.S. Provisional Application No. 61/244,049, filed Sep. 20, 2009, U.S.Provisional Application No. 61/244,050, filed Sep. 20, 2009, andco-pending U.S. Patent Application Publication No. 2012/0067008, eachincorporated by reference herein in their entirety, disclose methods forforming drug-eluting stents with hollow wires. Drug-eluting stentsformed with hollow wires can achieve similar elution curves asdrug-eluting stents with the therapeutic substance disposed in a polymeron the surface of the stent. Drug-eluting stents formed with hollowwires achieving similar elution curves as drug-polymer coated stent areexpected to have similar clinical efficacy while simultaneously beingsafer without the polymer coating. In addition, a variety of elutioncurves can be achieved from drug-eluting stents formed with hollowwires. In some applications, such as coronary stents, the diameter ofthe hollow wire lumen to be filled with the drug or therapeuticsubstance is extremely small, e.g. about 0.0015 in., which may makefilling the lumen difficult. As such, improved apparatus for and methodsof filling or loading a therapeutic substance or drug within a lumen ofa hollow wire of a stent are needed.

BRIEF SUMMARY OF THE INVENTION

Embodiments hereof are directed to methods and apparatus for filling afluid drug formulation within a lumenal space of a hollow wire having aplurality of side openings along a length thereof that forms adrug-eluting stent with a plurality of side drug delivery openings. Inan embodiment hereof, an apparatus includes a first chamber, a secondchamber, and a valve positioned between the first and second chambers.The first chamber houses a stent suspension means operable to suspend aplurality of stents. The second chamber houses a fluid drug formulation.The valve is operable to alternate between an open configuration inwhich the first chamber and second chamber are in fluid communicationand a closed configuration in which the first chamber and second chamberare not in fluid communication. The stent suspension means is operableto move the plurality of stents between the chambers. The first chambermay also house a reservoir of the same solvent of the fluid drugformulation. In addition, the second chamber may also house a wickingmeans in contact with the fluid drug formulation, and the wicking meansis operable to assist in the movement of the fluid drug formulation fromthe second chamber into the lumenal spaces of the stents by capillaryaction.

BRIEF DESCRIPTION OF DRAWINGS

The foregoing and other features and advantages of the invention will beapparent from the following description of embodiments hereof asillustrated in the accompanying drawings. The accompanying drawings,which are incorporated herein and form a part of the specification,further serve to explain the principles of the invention and to enable aperson skilled in the pertinent art to make and use the invention. Thedrawings are not to scale.

FIG. 1 is a side view of a drug eluting stent formed from a hollow wireaccording to one embodiment hereof.

FIG. 2A is a cross-sectional view taken along line 2A-2A of FIG. 1.

FIG. 2B is a sectional view taken along line 2B-2B at an end of thehollow wire of FIG. 1.

FIG. 2C is an end view taken along line 2C-2C of FIG. 1

FIG. 3 is a flow chart of a method for filling a plurality of stents ofFIG. 1 with a fluid drug formulation via capillary action.

FIGS. 4A-7 are schematic illustrations of the method of the flow chartof FIG. 3 performed in an apparatus having upper and lower chambers,wherein the stents come into contact with the fluid drug formulation viaa wicking means.

FIGS. 8A-8B illustrate an embodiment of a stent suspension means, whichholds or secures the plurality of stents in place during the capillaryfilling procedure described in FIGS. 4A-7.

FIGS. 9A-9B illustrate another embodiment of a stent suspension means,which holds or secures the plurality of stents in place during thecapillary filling procedure described in FIGS. 4A-7.

FIG. 10 illustrates another embodiment of a stent suspension means,which holds or secures the plurality of stents in place during thecapillary filling procedure described in FIGS. 4A-7.

FIG. 11 illustrates another embodiment of a stent suspension means,which holds or secures the plurality of stents in place during thecapillary filling procedure described in FIGS. 4A-7.

FIGS. 12A-12B illustrate another embodiment of a stent suspension means,which holds or secures the plurality of stents in place during thecapillary filling procedure described in FIGS. 4A-7.

FIGS. 13A-13B illustrate another embodiment of a stent suspension means,which holds or secures the plurality of stents in place during thecapillary filling procedure described in FIGS. 4A-7.

FIGS. 13C-13D illustrate another embodiment of a stent suspension means,which holds or secures the plurality of stents in place during thecapillary filling procedure described in FIGS. 4A-7.

FIGS. 14A-14B illustrate another embodiment of a stent suspension means,which holds or secures the plurality of stents in place during thecapillary filling procedure described in FIGS. 4A-7.

FIGS. 15A-15B illustrate another embodiment of a stent suspension means,which holds or secures the plurality of stents in place during thecapillary filling procedure described in FIGS. 4A-7.

FIG. 16 illustrates another embodiment of a stent suspension means,which holds or secures the plurality of stents in place during thecapillary filling procedure described in FIGS. 4A-7.

FIG. 17 illustrates another embodiment of a stent suspension means,which holds or secures the plurality of stents in place during thecapillary filling procedure described in FIGS. 4A-7.

FIGS. 18A-18B illustrate another embodiment of a stent suspension means,which holds or secures the plurality of stents in place during thecapillary filling procedure described in FIGS. 4A-7.

FIGS. 18C-18D illustrate another embodiment of a stent suspension means,which holds or secures the plurality of stents in place during thecapillary filling procedure described in FIGS. 4A-7.

FIGS. 19A-19D illustrate another embodiment of a stent suspension means,which holds or secures the plurality of stents in place during thecapillary filling procedure described in FIGS. 4A-7.

FIG. 20 illustrates another embodiment of a stent suspension means,which holds or secures the plurality of stents in place during thecapillary filling procedure described in FIGS. 4A-7.

FIGS. 21-21A illustrates another embodiment of a stent suspension means,which holds or secures the plurality of stents in place during thecapillary filling procedure described in FIGS. 4A-7.

FIGS. 22A-22C illustrate another embodiment of a stent suspension means,which holds or secures the plurality of stents in place during thecapillary filling procedure described in FIGS. 4A-7.

FIGS. 23A-B illustrate an embodiment of a wicking means, which controlstransfer of a fluid drug formulation to a stent during the capillaryfilling procedure described in FIGS. 4A-7.

FIG. 24 illustrates another embodiment of a wicking means, whichcontrols transfer of a fluid drug formulation to a stent during thecapillary filling procedure described in FIGS. 4A-7.

FIG. 25 illustrates another embodiment of a wicking means, whichcontrols transfer of a fluid drug formulation to a stent during thecapillary filling procedure described in FIGS. 4A-7.

FIG. 26 illustrates another embodiment of a wicking means, whichcontrols transfer of a fluid drug formulation to a stent during thecapillary filling procedure described in FIGS. 4A-7.

FIGS. 27A-27B illustrate another embodiment of a wicking means, whichcontrols transfer of a fluid drug formulation to a stent during thecapillary filling procedure described in FIGS. 4A-7.

FIG. 28 illustrates another embodiment of a wicking means, whichcontrols transfer of a fluid drug formulation to a stent during thecapillary filling procedure described in FIGS. 4A-7.

FIG. 29 illustrates another embodiment of a wicking means, whichcontrols transfer of a fluid drug formulation to a stent during thecapillary filling procedure described in FIGS. 4A-7.

FIG. 30 illustrates another embodiment of a wicking means, whichcontrols transfer of a fluid drug formulation to a stent during thecapillary filling procedure described in FIGS. 4A-7.

FIGS. 31A-31B illustrate another embodiment of a wicking means, whichcontrols transfer of a fluid drug formulation to a stent during thecapillary filling procedure described in FIGS. 4A-7.

FIGS. 32A-32B illustrate another embodiment of a wicking means, whichcontrols transfer of a fluid drug formulation to a stent during thecapillary filling procedure described in FIGS. 4A-7.

FIG. 33 illustrates another embodiment of a wicking means, whichcontrols transfer of a fluid drug formulation to a stent during thecapillary filling procedure described in FIGS. 4A-7.

FIG. 34 illustrates another embodiment of a wicking means, whichminimizes the contact area between each stent and the fluid drugformulation in order to control transfer of a fluid drug formulation toa stent during the capillary filling procedure described in FIGS. 4A-7.

FIG. 35 illustrates another embodiment of a wicking means, whichminimizes the contact area between each stent and the fluid drugformulation in order to control transfer of a fluid drug formulation toa stent during the capillary filling procedure described in FIGS. 4A-7.

FIGS. 36A-36C illustrate another embodiment of a wicking means, whichminimizes the contact area between each stent and the fluid drugformulation in order to control transfer of a fluid drug formulation toa stent during the capillary filling procedure described in FIGS. 4A-7.

FIGS. 37A-37C illustrate another embodiment of a wicking means, whichminimizes the contact area between each stent and the fluid drugformulation in order to control transfer of a fluid drug formulation toa stent during the capillary filling procedure described in FIGS. 4A-7.

FIGS. 38A-38B illustrate another embodiment of a wicking means, whichminimizes the contact area between each stent and the fluid drugformulation in order to control transfer of a fluid drug formulation toa stent during the capillary filling procedure described in FIGS. 4A-7.

FIG. 39 is a schematic illustration of an apparatus having upper andlower chambers for performing the method of the flow chart of FIG. 3,wherein the stents come into direct contact with the fluid drugformulation without the assistance of a wicking means.

DETAILED DESCRIPTION OF THE INVENTION

Specific embodiments of the present invention are now described withreference to the figures, wherein like reference numbers indicateidentical or functionally similar elements. The terms “distal” and“proximal” are used in the following description with respect to aposition or direction relative to the treating clinician. “Distal” or“distally” are a position distant from or in a direction away from theclinician. “Proximal” and “proximally” are a position near or in adirection toward the clinician. In addition, the term “self-expanding”is used in the following description is intended to convey that thestructures are shaped or formed from a material that can be providedwith a mechanical memory to return the structure from a compressed orconstricted delivery configuration to an expanded deployedconfiguration. Non-exhaustive exemplary self-expanding materials includestainless steel, a pseudo-elastic metal such as a nickel titanium alloyor nitinol, various polymers, or a so-called super alloy, which may havea base metal of nickel, cobalt, chromium, or other metal. Mechanicalmemory may be imparted to a wire or stent structure by thermal treatmentto achieve a spring temper in stainless steel, for example, or to set ashape memory in a susceptible metal alloy, such as nitinol. Variouspolymers that can be made to have shape memory characteristics may alsobe suitable for use in embodiments hereof to include polymers such aspolynorborene, trans-polyisoprene, styrene-butadiene, and polyurethane.As well, poly L-D lactic copolymer, oligo caprylactone copolymer andpoly cyclo-octine can be used separately or in conjunction with othershape memory polymers.

The following detailed description is merely exemplary in nature and isnot intended to limit the invention or the application and uses of theinvention. Drug eluting stents described herein may be utilized in thecontext of treatment of blood vessels such as the coronary, carotid andrenal arteries, or any other body passageways where it is deemed useful.More particularly, drug eluting stents loaded with a therapeuticsubstance by methods described herein are adapted for deployment atvarious treatment sites within the patient, and include vascular stents(e.g., coronary vascular stents and peripheral vascular stents such ascerebral stents), urinary stents (e.g., urethral stents and ureteralstents), biliary stents, tracheal stents, gastrointestinal stents andesophageal stents. Furthermore, there is no intention to be bound by anyexpressed or implied theory presented in the preceding technical field,background, brief summary or the following detailed description.

Hollow Wire Drug-Eluting Stent

An embodiment of a stent 100 to be loaded with a drug in accordance withembodiments hereof is shown in FIGS. 1-2C. Stent 100 is formed from ahollow strut or wire 102 and hereinafter may be referred to as a stentor a hollow core stent. Hollow wire 102 defines a lumen or lumenal space103, which may be formed before or after being shaped into a desiredstent pattern. In other words, as used herein, “a stent formed from ahollow wire” includes a straight hollow wire shaped into a desired stentpattern or a stent constructed from any suitable manufacturing methodthat results in a tubular component formed into a desired stent pattern,the tubular component having a lumen or lumenal space extendingcontinuously there through. As shown in FIG. 1, hollow wire 102 isformed into a series of generally sinusoidal waves including generallystraight segments 106 joined by bent segments or crowns 108 to form awaveform that is wound around a mandrel or other forming device to forma generally cylindrical stent 100 that defines a central blood flowpassageway or lumen 113 (shown in FIG. 2C) there through that extendsfrom a first end or tip 105 to a second end or tip 107 of stent 100.Selected crowns 108 of longitudinally adjacent turns of the waveform maybe joined by, for example, fusion points or welds 110 as shown inFIG. 1. Methods of filling a drug within a stent in accordance withembodiments hereof are not limited to stents having the pattern shown inFIG. 1. Stents formed into any pattern suitable for use as a stent maybe loaded with a drug by the methods disclosed herein. For example, andnot by way of limitation, stents formed into patterns disclosed in U.S.Pat. No. 4,886,062 to Wiktor, U.S. Pat. No. 5,133,732 to Wiktor, U.S.Pat. No. 5,782,903 to Wiktor, U.S. Pat. No. 6,136,023 to Boyle, and U.S.Pat. No. 5,019,090 to Pinchuk, each of which is incorporated byreference herein in its entirety, may be loaded with a drug by themethods disclosed herein.

As shown in FIG. 2A, hollow wire 102 of stent 100 allows for atherapeutic substance or drug 112 to be deposited within lumen orlumenal space 103 of hollow wire 102. Although lumen 103 is shown asuniformly filled with therapeutic substance or drug 112 in FIG. 2A,therapeutic substance or drug 112 is not required to fill or beuniformly dispersed within the lumenal space 103 of hollow wire 102 butis only required to occupy at least a portion of the lumenal space.Lumen 103 may continuously extend from a first end 114 to a second end114′ of hollow wire 102. Although hollow wire 102 is shown as generallyhaving a circular cross-section, hollow wire 102 may be generallyelliptical or rectangular in cross-section. Hollow wire 102 may have awall thickness W_(T) in the range of 0.0004 to 0.005 inch with an inneror lumen diameter I_(D) ranging from 0.0005 to 0.02 inch. Hollow wire102 that forms stent 100 may be made from a metallic material forproviding artificial radial support to the wall tissue, including butnot limited to stainless steel, nickel-titanium (nitinol), nickel-cobaltalloy such as MP35N, cobalt-chromium, tantalum, titanium, platinum,gold, silver, palladium, iridium, and the like. Alternatively, hollowwire 102 may be made from a hypotube, which is a hollow metal tube of avery small diameter of the type typically used in manufacturinghypodermic needles. Alternatively, hollow wire 102 may be formed from anon-metallic material, such as a polymeric material. The polymericmaterial may be biodegradable or bioresorbable such that stent 100 isabsorbed in the body after being utilized to restore patency to thelumen and/or provide drug delivery.

Hollow wire 102 further includes drug-delivery side openings or ports104 dispersed along its length to permit therapeutic substance or drug112 to be released from lumen 103. Side openings 104 may be disposedonly on generally straight segments 106 of stent 100, only on crowns 108of stent 100, or on both generally straight segments 106 and crowns 108.Side openings 104 may be sized and shaped as desired to control theelution rate of drug 112 from stent 100. More particularly, sideopenings 104 may be slits or may be holes having any suitablecross-section including but not limited to circular, oval, rectangular,or any polygonal cross-section. Larger sized side openings 104 generallypermit a faster elution rate and smaller sized side openings 104generally provide a slower elution rate. Further, the size and/orquantity of side openings 104 may be varied along stent 100 in order tovary the quantity and/or rate of drug 112 being eluted from stent 100 atdifferent portions of stent 100. Side openings 104 may be, for exampleand not by way of limitation, 5-30 μm in width or diameter. Sideopenings 104 may be provided only on an outwardly facing or ablumenalsurface 116 of stent 100, as shown in FIG. 2, only on the inwardlyfacing or lumenal surface 118 of stent 100, on both surfaces, or may beprovided anywhere along the circumference of wire 102.

In various embodiments hereof, a wide range of therapeutic agents ordrugs may be utilized as the elutable therapeutic substance or drug 112contained in lumen 103 of hollow wire 102, with the pharmaceuticallyeffective amount being readily determined by one of ordinary skill inthe art and ultimately depending, for example, upon the condition to betreated, the nature of the therapeutic agent itself, the tissue intowhich the dosage form is introduced, and so forth. Further, it will beunderstood by one of ordinary skill in the art that one or moretherapeutic substances or drugs may be loaded into hollow wire 102.Therapeutic substance or drug 112 delivered to the area of a stenoticlesion can be of the type that dissolves plaque material forming thestenosis or can be an anti-platelet formation drug, an anti-thromboticdrug, or an anti-proliferative drug. Such drugs can include TPA,heparin, urokinase, sirolimus or analogues of sirolimus, for example. Ofcourse stent 100 can be used for delivering any suitable medications tothe walls and interior of a body vessel including one or more of thefollowing: anti-thrombotic agents, anti-proliferative agents,anti-inflammatory agents, anti-migratory agents, agents affectingextracellular matrix production and organization, antineoplastic agents,anti-mitotic agents, anesthetic agents, anti-coagulants, vascular cellgrowth promoters, vascular cell growth inhibitors, cholesterol-loweringagents, vasodilating agents, and agents that interfere with endogenousvasoactive mechanisms.

In accordance with embodiments hereof, stent 100 is loaded or filledwith therapeutic substance or drug 112 prior to implantation into thebody. Therapeutic substance or drug 112 is generally mixed with asolvent or dispersion medium/dispersant in order to be loaded into lumen103 of hollow wire 102. In addition, the therapeutic substance or drug112 can be mixed with an excipient to assist with elution in addition tothe solvent or dispersion medium/dispersant in order to be loaded intolumen 103 of hollow wire 102. Hereinafter, the term “fluid drugformulation” may be used to refer generally to therapeutic substance ordrug 112, a solvent or dispersion medium, and anyexcipients/additives/modifiers added thereto. In one embodiment,therapeutic substance or drug 112 is mixed with a solvent or solventmixture as a solution before being loaded into hollow wire 102. Asolution is a homogeneous mixture in which therapeutic substance or drug112 dissolves within a solvent or a solvent mixture. In one embodiment,a solution includes a high-capacity solvent which is an organic solventthat has a high capacity to dissolve therapeutic substance or drug 112.High capacity as utilized herein is defined as an ability to dissolvetherapeutic substance or drug 112 at concentrations greater than 500 mgof substance per milliliter of solvent. Examples of high capacity drugdissolving solvents for sirolimus and similar substances include but arenot limited to tetrahydrofuran (THF), di-chloromethane (DCM),chloroform, and di-methyl-sulfoxide (DMSO). In addition to thehigh-capacity solvent, a solution may include an excipient in order toassist in drug elution. In one embodiment, an excipient may be asurfactant such as but not limited to sorbitan fatty acid esters such assorbitan monooleate and sorbitan monolaurate, polysorbates such aspolysorbate 20, polysorbate 60, and polysorbate 80, cyclodextrins suchas 2-hydroxypropyl-beta-cyclodextrin and2,6-di-O-methyl-beta-cyclodextrin, sodium dodecyl sulfate, octylglucoside, and low molecular weight poly(ethylene glycol)s. In anotherembodiment, an excipient may be a hydrophilic agent such as but notlimited to salts such as sodium chloride and other materials such asurea, citric acid, and ascorbic acid. In yet another embodiment, anexcipient may be a stabilizer such as but not limited to butylatedhydroxytoluene (BHT). Depending on the desired drug load, a low capacitysolvent can also be chosen for its reduced solubility of therapeuticsubstance or drug 112. Low capacity is defined as an ability to dissolvetherapeutic substance or drug 112 at concentrations typically below 500mg of drug per milliliter solvent. Examples of low capacity drugdissolving solvents for sirolimus and similar substances include but arenot limited to methanol, ethanol, propanol, acetonitrile, ethyl lactate,acetone, and solvent mixtures like tetrahydrofuran/water (9:1 weightratio). After a solution is loaded into stent 100, therapeutic substanceor drug 112 may be precipitated out of the solution, e.g., transformedinto solid phase, and the majority of the residual solvent and anynonsolvent, if present, may be extracted from the lumenal space ofhollow wire 102 such that primarily only therapeutic substance or drug112 or therapeutic substance or drug 112 and one or more excipientsremain to be eluted into the body.

In another embodiment, therapeutic substance or drug 112 is mixed with adispersion medium as a slurry/suspension before being loaded into hollowwire 102. In a slurry/suspension form, therapeutic substance or drug 112is not dissolved but rather dispersed as solid particulate in adispersion medium, which refers to a continuous medium in liquid formwithin which the solid particles are dispersed. Examples of dispersionmediums with an inability to dissolve therapeutic substance or drug 112depend on the properties of therapeutic substance or drug 112. Forexample, suitable dispersion mediums with an inability to dissolvesirolimus include but are not limited to water, hexane, and other simplealkanes, e.g., C5 thru C10. Certain excipients, suspending agents,surfactants, and/or other additives/modifiers can be added to the drugslurry/suspension to aid in suspension and stabilization, ensure an evendispersion of drug throughout the suspension and/or increase the surfacelubricity of the drug particles. Surfactants thus generally preventtherapeutic substance or drug 112 from floating on the top of or sinkingto the bottom of the dispersion medium. Examples of surfactants includebut are not limited to sorbitan fatty acid esters such as sorbitanmonooleate and sorbitan monolaurate, polysorbates such as polysorbate20, polysorbate 60, and polysorbate 80, and cyclodextrins such as2-hydroxypropyl-beta-cyclodextrin and 2,6-di-O-methyl-beta-cyclodextrin.In one embodiment, the targeted amount of therapeutic substance or drug112 is suspended in the dispersion medium and the appropriateadditive/modifier is added on a 0.001 to 10 wt % basis of totalformulation. In addition, an excipient such as urea or2,6-di-O-methyl-beta-cylcodextrin may be added to the slurry/suspensionin order to assist in drug elution.

Open ends 114, 114′ of wire 102 may be closed or sealed either before orafter the drug is loaded within lumen 103 as shown in the sectional viewof FIG. 2B, which is taken along line 2B-2B of FIG. 1. Once positionedinside of the body at the desired location, stent 100 is deployed forpermanent or temporary implantation in the body lumen such thattherapeutic substance or drug 112 may elute from lumen 103 via sideopenings 104.

Filling Process Via Capillary Action

Embodiments hereof relate to the use of capillary action to fill lumen103 of hollow wire 102. Capillary action as used herein relates to theability of a liquid to flow in narrow spaces without the assistance of,and in opposition to, external forces like gravity. As will be explainedin further detail herein, only a portion of stent 100 having at leastone side hole 104 is required to be submerged or exposed to a fluid drugformulation, or submerged or exposed to a wicking means in contact witha fluid drug formulation. The fluid drug formulation will then wick ortravel into lumen 103 of hollow wire 102 via submerged/exposed holes 104and fill or load the entire length of lumen 103 via capillary action.Capillary action occurs because of inter-molecular attractive forcesbetween the fluid drug formulation and hollow wire 102. When lumen 103of hollow wire 102 is sufficiently small, then the combination ofsurface tension and adhesive forces formed between the fluid drugformulation and hollow wire 102 act to lift the fluid drug formulationand fill the hollow wire. Filling stents 100 via capillary action resultin a filling method that streamlines the drug filling process becausesuch a method may be utilized to batch fill a plurality of stents in arelatively short time period. In addition, filling stents 100 viacapillary action reduces drug load variability and makes the drug fillprocess more controllable and predictable. Capillary action results influid drug formulation uniformly filling or deposited within lumen 103of hollow wire 102, and after solvent/dispersion medium extraction whichis described in more detail below, lumen 103 of hollow wire 102 has auniform drug content along its length.

More particularly, FIG. 3 is a flow chart of a method for filling lumen103 of a stent 100 with a fluid drug formulation 432 via capillaryaction. FIG. 3 will be described in conjunction with FIGS. 4A-7, whichare schematic illustrations of an apparatus 420 which may be utilized toperform the method steps of FIG. 3. As will be described in more detailherein, FIGS. 4A-7 represent an embodiment hereof in which a wickingmeans controls the transfer of fluid drug formulation into lumen 103while FIG. 39 represents an embodiment hereof in which the stentsdirectly contact fluid drug formulation without a wicking means in orderto fill lumen 103. For illustrative purposes only, stents 100 arerepresented as straight tubular structures in FIGS. 4A-7 although itwill be understood by one of ordinary skill in the art that stents 100are a hollow wire shaped into a desired stent pattern as previouslydescribed with reference to FIG. 1. Apparatus 420 includes a first orupper chamber 422 which houses a manifold or stent suspension means 428and an open container or reservoir 431 filled with a liquid or fluidsolvent 433, a second or lower chamber 424 which houses a wicking means430 that is in contact with fluid drug formulation 432 that includestherapeutic substance or drug 112, and a valve 426 positioned betweenupper chamber 422 and lower chamber 424. Solvent 433 within reservoir431 is the same solvent as used in fluid drug formulation 432. Valve 426is operable to alternate between an open configuration in which thefirst chamber and second chamber are in fluid communication, and aclosed configuration in which the first chamber and second chamber arenot in fluid communication. A plurality of stents 100 are loaded ontostent suspension means 428, which holds or suspends them in place duringthe capillary filling procedure, as shown in step 301A of FIG. 3. Stentsuspension means 428 may suspend stents 100 in a vertical orientation asshown in FIG. 4A, or alternatively may suspend stents 100 in ahorizontal orientation as shown in FIG. 4B. Stent suspension means 428is operable to move the plurality of stents 100 between upper and lowerchambers 422, 424. The capillary filling procedures in accordance withembodiment hereof may be readily scalable as batch processes. Whenloaded onto stent suspension means 428, stents 100 are already formed,that is, hollow wire 102 has previously been shaped or formed into adesired waveform and formed into cylindrical stent 100 as describedabove with respect to FIG. 1. Alternatively, if desired, the capillaryfilling process may be performed on straight hollow wires prior toshaping or forming hollow wire 102 into the desired waveform andsubsequent stent configuration. As will be explained in more detailherein, in an embodiment hereof, stent suspension means 428 holds stents100 in place by slightly expanding the inner diameter of the stents,thereby increasing friction between the stents and stent suspensionmeans 428 and minimizing undesired movement of the stents.

Prior to the initiation of capillary filling, with reference to FIG. 4Aand/or FIG. 4B, valve 426 is closed such that first or upper chamber 422and second or lower chamber 424 are distinct or separate closed chambersand not in fluid communication with each other. A pressure source 434and a heat source 435 are connected to the interior of the upper chamber422. In another embodiment (not shown), pressure source 434 and/or heatsource 435 are connected to the interior of lower chamber 424, dependingon the relative volume and mass differences between the chambers. Beforeplacing stents 100 into upper chamber 422, pressure source 434 is usedto purge any residual solvent vapor from the upper chamber. After thepurge, stent suspension means 428 holding stents 100 are placed intoupper chamber 422 and pressure source 434 is stopped to allow solventvapor to fill upper chamber 422, as shown in step 301B of FIG. 3. Whenevaporation has stopped or sufficiently slowed, valve 426 is opened andso that upper and lower chambers 422, 424 are exposed to each other andin fluid communication as shown in step 301C of FIG. 3 and as shown inFIG. 5. Both upper and lower chambers 422, 424 are then required toreach solvent vapor saturation or near solvent vapor saturation, asshown in step 301D of FIG. 3. Stated another way, both upper and lowerchambers 422, 424 are required to reach the vapor-liquid equilibrium ofsolvent 433 of fluid drug formulation 432 or near the vapor-liquidequilibrium of solvent 433. Vapor-liquid equilibrium is the condition orstate where a liquid and its vapor are in equilibrium with each other,where the rate of evaporation equals the rate of condensation such thatthere is no net or mass transport across its respective phase. Such anequilibrium is practically reached in a relatively closed location if aliquid and its vapor are allowed to stand in contact with each other fora sufficient time period. As used herein, the term “near thevapor-liquid equilibrium” or “near solvent vapor saturation” includespressure rates within a range of −5 torr/min to 5 torr/min. Evaporationis considered very slow and practically negligible within this range ofpressure rates, and the filling process may be performed within thisrange of pressure rates without premature precipitation of therapeuticsubstance or drug 112 within lumen 103 of hollow wire 102. In apreferred embodiment hereof, the filling process is performed when thepressure rate in between −2 torr/min to 2 torr/min. Due to the step ofallowing evaporation in the first or upper chamber 422 to stop orsufficiently slow prior to opening valve 426, evaporation of fluid drugformulation 432 within second or lower chamber 424 is minimized suchthat the formulation concentration does not change.

There are several ways to reduce the amount of time required to reachsolvent vapor saturation of chambers 422, 424, thereby reducing overallprocessing time to increase throughput. In one embodiment, a largesurface area is created to reduce the amount of time required to reachvapor saturation. In an embodiment, a large surface area may be createdby atomizing droplets within upper and/or lower chamber 422, 424 withultrasonic spray nozzles. In another embodiment, a large surface areamay be created by providing wicking means 430 with a large surface areaas shown in FIGS. 4A-7 in order to increase the surface area of theevaporating solvent. The amount of time required to reach vaporsaturation may also be reduced by increasing the temperature of thesolvent/dispersion medium. Since solvent vapor pressure is usually verydependent on temperature, heat source 435 (which may alternatively belocated within second lower chamber 424) may be utilized to control thetemperature of fluid drug formulation 432. The amount of time requiredto reach vapor saturation may also be reduced by via convection of gasacross the solvent surface. For example, a fan 499 may be utilized inupper chamber 422 to create convection across reservoir 431 containing asupply of solvent 433. Reservoir 431 of solvent 433 thus supplies thevapor required to reach solvent vapor saturation. The above-describedmethods for reducing the amount of time required to reach solvent vaporsaturation of chambers 422, 424 may be used individually or in anycombination thereof.

Once both chambers 422, 424 are at or near solvent vapor saturation,capillary filling may be initiated by moving stents 100 into contactwith or submersed into wicking means 430 as shown in step 301E of FIG. 3and as shown in FIG. 6. Wicking means 430 is in contact with fluid drugformulation 432, to control transfer of the fluid drug formulation intolumen 103 of hollow wire 102 of stent 100. In one embodiment, wickingmeans 430 is an open-celled polyurethane sponge or foam although variousalternative embodiments of the wicking means are discussed herein.Stents 100 are pushed into or onto wicking means 430, thereby deformingwicking means 430. As the wicking means deforms, wicking means 430transfers fluid drug formulation 432 from lower chamber 424 intosubmersed holes 104 of stent 100. Lumen 103 of hollow wire 102 of stent100 is filled by surface tension driving fluid drug formulation 432through the stent lumen, until the entire length of lumen 103 is filledvia capillary action forces, as shown in step 301F of FIG. 3. During thefilling step, chambers 422, 424 are maintained at or near thevapor-liquid equilibrium of solvent 433 such that evaporation does notprecipitate therapeutic substance or drug 112 as fluid drug formulation432 fills lumen 103 of hollow wire 102 of stents 100.

FIGS. 6A-6C are schematic illustrations of a portion of a stent 100submersed or in contact with wicking means 430 to demonstrate thecapillary filling process. Notably, only a portion of each stent havingat least one side hole or port 104 is required to be submersed intowicking means 430. As such, a minimal amount of the exterior surfaces ofwires 102 of stents 100 are exposed to the fluid drug formulation andmost of the exterior surface of the hollow wire of the stent is neverexposed to the fluid drug formulation, therefore not requiringadditional cleaning or removal of drug residue. FIG. 6A corresponds toFIG. 4A, in which stent suspension means 428 hold stents 100 in avertical orientation. When held vertically, only a tip 107 of each stent100 is submersed into wicking means 430 such that at least one side hole104 is in contact with wicking means 430 and exposed to fluid drugformulation 432. For example, in an embodiment, approximately 0.3 mm ofthe length of each stent is exposed or driven into to the wicking means.FIG. 6B corresponds to FIG. 4B, in which stent suspension means 428 holdstents 100 in a horizontal orientation. When held horizontally, alongitudinal strip or segment 611 along an outer surface of each stent100 is submersed into wicking means 430 such that at least one side hole104 is in contact with wicking means 430 and exposed to fluid drugformulation 432. Regardless of how stents 100 are oriented, fluid drugformulation 432 passes through hole(s) 104 on hollow wire 102 that arein contact with wicking means 430 as shown in FIG. 6C, which illustratesonly a portion of hollow wire 102 having a side hole 104 submersed intowicking means 430. Fluid drug formulation 432 forms a concave meniscuswithin lumen 103 of hollow wire 102. Adhesion forces pull fluid drugformulation 432 up until there is a sufficient mass of fluid drugformulation 432 present for gravitational forces to overcome theintermolecular forces between fluid drug formulation 432 and hollow wire102, or the advancing fluid column completely fills the lumen. Theheight h of a column of fluid drug formulation 432 is determined byh−2γ cos 8/ρgr,

where γ is the liquid-air surface tension (force/unit length), θ is thecontact angle, ρ is the density of fluid drug formulation 432(mass/volume), g is local gravitational field strength (force/unitmass), and r is the radius of hollow wire 102 (length). Due to thenature of capillary filling and the intermolecular forces between fluiddrug formulation 432 and hollow wire 102, fluid drug formulation 432does not exit or leak out of non-submersed holes or ports 104 that occuralong the length of the stent as fluid drug formulation 432 fills lumen103 of hollow wire 102.

The time required to fill the entire length of lumen 103 of hollow wire102 of stent 100 depends upon the stent configuration and length. Filltime depends upon various factors, including but not limited to thelength of hollow wire 102, the size of holes 104, the number ofsubmersed holes 104, the size of lumen 103, and the properties of fluiddrug formulation 432. For example, in an embodiment in which 0.3 mmlength of a vertically-oriented 3 mm×18 mm stent is placed into contactwith an open-celled polyurethane sponge wicking means, which is incontact with a fluid drug formulation including rapamycin dissolved inmethanol, filling time is approximately 22 minutes. If it is desired toreduce the overall fill time, the number of submersed holes 104 may beincreased. Often, horizontal orientation of stents may be utilized if itis desired to place a greater number of side holes into contact with thewicking means and thereby reduce the overall fill time. However,horizontal orientation of stents may expose a greater amount of theexterior surfaces of wires 102 of stents 100 to the fluid drugformulation.

After lumen 103 is completely filled, with reference to FIG. 7, stents100 are retracted or pulled up such that stents 100 are no longer incontact with wicking means 430. As stents 100 are retracted out ofwicking means 430, wicking means 430 removes excess fluid drugformulation 432 from the exterior surfaces of wires 102 of stents 100such that stents 100 are free or substantially free of drug residue ontheir exterior surfaces, leaving fluid drug formulation 432 only withinlumen 103 of hollow wire 102 of stent 100. The final step of thecapillary action filling process includes extracting the solvent ordispersion medium of fluid drug formulation 432 from within the lumenalspace, thereby precipitating the solute, i.e., therapeutic substance ordrug 112, within lumen 103 and creating a drug-filled stent 100 withprimarily only therapeutic substance or drug 112 and one or moreexcipients within stent 100 to be eluted into the body. Moreparticularly, stents 100 are retracted into upper chamber 422, which isstill at or near vapor-liquid equilibrium of solvent 433, as shown instep 301G of FIG. 3. Valve 426 is then closed such that the chambers422, 424 are no longer in fluid communication as shown in step 301H ofFIG. 3 and as shown in FIG. 7. Valve 426 is closed to isolate fluid drugformulation 432 from the upper chamber 422 so that evaporation does notoccur from the fluid drug formulation and additional batches of stentsmay be filled with the same fluid drug formulation without concentrationchanges. Upper chamber 422 is then vented to reduce its solvent vaporpressure back to ambient pressure, as shown in step 301I of FIG. 3. Asthe solvent vapor pressure is reduced in the upper chamber, evaporationwithin lumen 103 of hollow wire 102 is initiated and the solvent of drugfluid formulation 432 is removed, thereby precipitating itsconstituents. After the solvent or dispersion medium is removed fromlumen 103, therapeutic substance or drug 112 fills at least a portion oflumen 103. Stents 100 may then be removed from apparatus 420.

Means for Holding Stents

FIGS. 8A-22B illustrate several embodiments of stent suspension means428, which holds or secures the plurality of stents in place during thecapillary filling procedure as described with reference to FIGS. 4A-7.Stent suspension means 428 serves several functions, including holdingone or more stents in such a manner that only a portion of stents 100are exposed to fluid drug formulation 432. In addition, stent suspensionmeans 428 is preferably configured to simultaneously hold a plurality ofstents 100 such that the batch size of a capillary filling procedure isreadily scalable. In embodiments described below, the stent suspensionmeans firmly and securely holds stents 100 in place by slightlyexpanding the inner diameter of the stents and deforming elastically,thereby increasing friction between the stents and the stent suspensionmeans and minimizing undesired movement of the stents. When stents 100are being positioned on stent suspension means 428, stents 100 may besecured in an array (not shown) having a plurality of wells each sizedto accommodate. The array may be positioned in first or upper chamber422 of apparatus 420, and is configured to hold stents 100 stationarywhile stent suspension means 428 are operated as described herein tohold stents 100 in place during the filling process. For illustrativepurposes only, stents 100 are represented as straight tubular structuresin FIGS. 8A-22B although it will be understood by one of ordinary skillin the art that stents 100 are a hollow wire shaped into a desired stentpattern as previously described with reference to FIG. 1. In addition,for illustrative purposes, the stent suspension means described in FIGS.8A-22B are shown as holding stent 100 in a vertical orientation but maybe modified to hold stent 100 in a horizontal orientation as describedherein with reference to FIG. 4B.

FIGS. 8A and 8B depict a stent suspension means 828 that includes aheader or carousel 836, a portion of which is shown in the figure, and amandrel wire 850 for holding a stent 100 in place during the capillaryfilling procedure described with reference to FIGS. 4A-7. Although onlyone mandrel wire 850 is shown, it will be understood by one of ordinaryskill in the art that a plurality of mandrel wires may be coupled orattached to header or carousel 836 for accommodating a plurality ofstents 100. Header or carousel 836 is a generally flat sheet-likecomponent having at least one hole or passageway 837 formed therethrough to allow for passage of mandrel 850. Mandrel wire 850 is anelongated component having a first end 840 fixed above header orcarousel 836 and a second end 842 movable relative to header or carousel836. Mandrel wire 850 extends through a tubular component or shaft 815,which is coupled or attached to header 836 such that a lumen thereof isaligned with a passageway 837. Mandrel wire 850 extends through thelumen of shaft 815, with both first and second ends 840, 842 extendingout of a top or first end thereof. Second end 842 of mandrel wire 850may be advanced to cause a loop 838 thereof to extend out of a second orbottom end of shaft 815. Loop 838 becomes larger or smaller based on aposition of second end 842 relative to shaft 815. In operation, stent100 is positioned over shaft 815, with mandrel wire 850 being containedwithin the shaft as shown in FIG. 8A. Once stent 100 is in position,second end 842 is moved toward header or carousel 836 in a “downward”direction, as indicated by directional arrow 839, towards stent 100, toexpose loop 828 out of shaft 815 and to increase or expand the diameterof loop 838 until the loop 838 abuts against or is in opposition withthe inner diameter of stent 100 as shown in FIG. 8B. The expanded loop838 thus grabs onto the inner diameter of stent 100, and in oneembodiment, may slightly expand the inner diameter of stent 100 toincrease friction between stent 100 and stent suspension means 828 tominimize undesired movement of stent 100. Loop 838 is formed from anelastic material, including but not limited to Nitinol or spring steel.

FIGS. 9A-9B illustrate another embodiment of a stent suspension means928 that includes a header or carousel 936, a portion of which is shownin the figure, and a loop 938 for holding a stent 100 in place duringthe capillary filling procedure described with reference to FIGS. 4A-7.Although only one wire loop 938 is shown, it will be understood by oneof ordinary skill in the art that a plurality of wire loops may becoupled to header or carousel 936 for accommodating a plurality ofstents 100. Header or carousel 936 is a generally flat sheet-likecomponent having a loop or u-shaped component 938 coupled thereto, witha first end 940 and a second end 942 of loop 938 both coupled orattached or bonded to header or carousel 936. A push-pull rod or wire944 has a first end coupled to loop 938, at approximately the midpointthereof, and a second end 948 which extends through a hole or passageway937 formed through header or carousel 936. Second end 948 of push-pullwire 944 may be pushed or pulled relative to header or carousel 936 toadjust the size or diameter of loop 938. In operation, second end 948 ofpush-pull wire 944 is positioned to form a relatively small diameterloop 938 that fits within the inner diameter of stent 100 as shown inFIG. 9A. Once in position, second end 948 of push-pull wire 944 is movedin an “upward” direction relative to header or carousel 936, asindicated by directional arrow 941, away from stent 100, causing loop938 to bow outwards. Movement of push-pull wire 944 causes the diameterof loop 938 to increase or expand until loop 938 abuts against or is inopposition with the inner diameter of stent 100 as shown in FIG. 9B. Thelarger, expanded loop 938 shown in FIG. 9B thus grabs onto the innerdiameter of stent 100, and in one embodiment, may slightly expand theinner diameter of stent 100 to increase friction between stent 100 andstent suspension means 928 to minimize undesired movement of stent 100.Loop 938 is formed from an elastic material, including but not limitedto Nitinol or spring steel. Although FIGS. 9A-9B are shown with only oneloop attached thereto for grabbing onto the inner diameter of stent 100,one or more additional loops may be provided and equally spaced aroundthe inner diameter of stent 100 to grab stent 100 in a morecircumferential manner.

FIG. 10 illustrates another embodiment of a stent suspension means 1028that includes a header or carousel 1036, a portion of which is shown inthe figure, and a mandrel 1050 for holding a stent 100 in place duringthe capillary filling procedure described with reference to FIGS. 4A-7.Although only one mandrel 1050 is shown, it will be understood by one ofordinary skill in the art that a plurality of mandrels may be coupled toheader or carousel 1036 for accommodating a plurality of stents 100.Header or carousel 1036 is a generally flat sheet-like component, and afirst end 1051 of mandrel 1050 is coupled or attached to header orcarousel 1036. Mandrel 1050 is a solid tubular component having an outerdiameter which is less than the inner diameter of stent 100, so thatmandrel 1050 fits inside stent 100 such that a second end 1053 ofmandrel 1050 extends within stent 100. Mandrel 1050 also includes a slotor passageway 1052 formed there through, and a removable dowel rod 1054extends through passageway 1052. Dowel rod 1054 has a length greaterthan the outer diameter of mandrel 1050, such that the ends of dowel rod1054 extend beyond or past the outer diameter of mandrel 1050. Thediameter of dowel rod 1054 is sufficiently small to pass throughopenings of stent 100 that are formed between the series of generallysinusoidal waves of stent 100. Stent 100 thus hangs on dowel rod 1054,being held in place by the interference between hollow wire 102 of stent100 and dowel rod 1054. Dowel rod 1054 and mandrel 1050 may be connectedby a slip fit or spring-release mechanism (not shown) that allows dowelrod 1054 to extrude out of the mandrel and through openings of thestent. Dowel rod 1054 and mandrel 1050 may be formed of any suitablematerial that is chemically compatible with organic solvents such as butnot limited to stainless steel, aluminum, or select polymers includingdelrin and polystyrene. In another embodiment (not shown), rather thanremovable dowel rod 1054, tabs or similar structures may be coupled tomandrel 1050 and extend perpendicular to the longitudinal axis of stent100 to pass through the openings of the stent.

FIG. 11 illustrates another embodiment of a stent suspension means 1128that includes a header or carousel 1136, a portion of which is shown inthe figure, and a mandrel 1150 for holding a stent 100 in place duringthe capillary filling procedure described with reference to FIGS. 4A-7.Although only one mandrel 1150 is shown, it will be understood by one ofordinary skill in the art that a plurality of mandrels may be coupled toheader or carousel 1136 for accommodating a plurality of stents 100.Header or carousel 1136 is a generally flat sheet-like component, and afirst end 1151 of mandrel 1150 is coupled or attached to header orcarousel 1136. Mandrel 1150 is a solid tubular component having malethreads 1155 formed on an exterior surface thereof, the male threadshaving an outer diameter which is approximately equal to or slightlygreater than the inner diameter of stent 100. Male threads 1155 engageor grip onto the inner diameter of stent 100, similar to a wood ordrywall screw. Male threads 1155 may be formed from steel, and may beintegrally formed on mandrel 1150 or may be a separate component coupledthereto.

FIGS. 12A-12B illustrate another embodiment of a stent suspension means1228 that includes a header or carousel 1236, a portion of which isshown in the figure, and a mandrel 1250 for holding a stent 100 in placeduring the capillary filling procedure described with reference to FIGS.4A-7. Although only one mandrel 1250 is shown, it will be understood byone of ordinary skill in the art that a plurality of mandrels may becoupled to header or carousel 1236 for accommodating a plurality ofstents 100. Header or carousel 1236 is a generally flat sheet-likecomponent having at least one hole or passageway 1237 formed therethrough to allow for passage of a portion of mandrel 1250. Mandrel 1250includes two concentric tubes or shafts, an outer tube 1256 and an innertube 1258 slidably mounted within a lumen 1257 defined by outer tube1256. A first end 1262 of outer tube 1256 is coupled to header orcarousel 1236, and inner tube 1258 is longer than outer tube 1256 suchthat a first end 1265 of inner tube 1258 extends beyond first end 1262of outer tube 1256 and through passageway 1237 of header or carousel1236 and a second end 1264 of inner tube 1258 extends beyond a secondend 1263 of outer tube 1256. A braided wire tubular or cylindricalcomponent 1260 has a first end 1259 coupled to second end 1263 of outertube 1256 and a second end 1261 coupled to second end 1264 of inner tube1258. Inner tube 1258 may be pushed or pulled relative to outer tube1256 to adjust the size or outer diameter of braided component 1260. Inoperation, second end 1265 of inner tube 1258 is positioned to fullyextend or lengthen braided component 1260 such that the diameter ofbraided component 1260 fits within the inner diameter of stent 100 asshown in FIG. 12A. Once stent 100 is in position as desired, second end1265 of inner tube 1258 is moved in an “upward” direction toward headeror carousel 1236, as indicated by directional arrow 1241, away fromstent 100, causing braided component 1260 to radially expand. Movementof inner tube 1258 relative to outer tube 1256 causes the diameter ofbraided component 1260 to increase or expand until braided component1260 abuts against or is in opposition with the inner diameter of stent100 as shown in FIG. 12B. The larger, braided component 1260 thus grabsonto the inner diameter of stent 100, and in one embodiment, mayslightly expand the inner diameter of stent 100 to increase frictionbetween stent 100 and stent suspension means 1228 to minimize undesiredmovement of stent 100. To release stent 100, inner tube 1258 is movedrelative to outer tube 1256 in an “downward” direction, toward stent100, to longitudinally extend braided component 1260 back to theposition shown in FIG. 12A. Braided component 1260 is formed from asuperelastic material, including but not limited to Nitinol or stainlesssteel, and tubes 1256, 1258 may be formed from stainless steel or apolymeric material such as but not limited to PEEK, polyimide, or PTFE.

FIGS. 13A-13B illustrate another embodiment of a stent suspension means1328 that includes a header or carousel 1336, a portion of which isshown in the figure, and a mandrel 1350 for holding a stent 100 in placeduring the capillary filling procedure described with reference to FIGS.4A-7. Although only one mandrel 1350 is shown, it will be understood byone of ordinary skill in the art that a plurality of mandrels may becoupled to header or carousel 1336 for accommodating a plurality ofstents 100. Header or carousel 1336 is a generally flat sheet-likecomponent having at least one hole or passageway 1337 formed therethrough to allow for passage of a portion of mandrel 1350. Mandrel 1350includes two concentric tubes or shafts that extend through passageway1337 of header or carousel 1336, an outer tube 1356 and an inner tube1358 slidably mounted to extend through a lumen 1357 defined by outertube 1356. Inner tube 1358 is longer than outer tube 1356 such that afirst end 1365 of inner tube 1358 extends beyond first end 1362 of outertube 1356 and a second end 1364 of inner tube 1358 extends beyond asecond end 1363 of outer tube 1356. Outer tube 1356 may be a Nitinoltube, and second end 1363 of outer tube 1356 includes a plurality offingers, similar to a collet. Second end 1364 of inner tube 1358 isbulbous or flared, meaning that it has an outer diameter which isgreater than the rest of inner tube 1358. The outer diameter of secondend 1364 of inner tube 1358 is greater than the inner diameter of outertube 1356. Inner tube 1358 may be pushed or pulled relative to outertube 1356 to radially deploy the fingers formed on second end 1363 ofouter tube 1356. In operation, second end 1365 of inner tube 1358 ispositioned such that the bulbous second end 1364 of inner tube 1358 isnot in contact with the fingers formed on second end 1363 of outer tube1356 as shown in FIG. 13A. Once stent 100 is in position as desired,second end 1364 of inner tube 1358 is moved in an “upward” directiontoward header or carousel 1336, as indicated by directional arrow 1341,away from stent 100, causing the bulbous second end 1364 of inner tube1358 to come into contact with the fingers formed on second end 1363 ofouter tube 1356. Bulbous second end 1364 of inner tube 1358 radiallydeploys and/or spreads out the fingers formed on second end 1363 ofouter tube 1356 until the fingers grab onto or abut against the innerdiameter of stent 100 as shown in FIG. 13B. In one embodiment, thedeployed fingers may slightly expand the inner diameter of stent 100 toincrease the friction between stent 100 and stent suspension means 1328to minimize undesired movement of stent 100.

FIGS. 13C-13D illustrate another embodiment of a stent suspension means1328C that includes header or carousel 1336, a portion of which is shownin the figure, and a mandrel 1350C for holding a stent 100 in placeduring the capillary filling procedure described with reference to FIGS.4A-7. Although only one mandrel 1350 is shown, it will be understood byone of ordinary skill in the art that a plurality of mandrels may becoupled to header or carousel 1336 for accommodating a plurality ofstents 100. As described with respect to FIG. 13A, header or carousel1336 is a generally flat sheet-like component having at least one holeor passageway 1337 formed there through to allow for passage of aportion of mandrel 1350C. Mandrel 1350C includes two concentric tubes orshafts that extend through passageway 1337C of header or carousel 1336C,an outer tube 1356C and an inner tube 1358C slidably mounted to extendthrough a lumen 1357C defined by outer tube 1356C. Outer tube 1356C maybe a Nitinol tube and a second end 1363C of outer tube 1356C includes aplurality of fingers, similar to a collet. In this embodiment, unlikethe embodiment of FIGS. 13A-B, the fingers formed on the second end1363C of outer tube 1356C may be initially curved or bent radiallyinward toward inner tube 1358C. At least a second end 1364C of innertube 1358C has a diameter only slightly less than the inner diameter ofouter tube 1356C. Inner tube 1358C may be pushed or pulled relative toouter tube 1356C to radially deploy the fingers formed on second end1363C of outer tube 1356C. In operation, second end 1365C of inner tube1358C is positioned such that the second end 1364C of inner tube 1358Cis not in contact with the fingers formed on second end 1363C of outertube 1356C as shown in FIG. 13C. Once stent 100 is in position asdesired, second end 1364C of inner tube 1358C is moved in a “downward”direction toward header or carousel 1336, as indicated by directionalarrow 1341C, towards stent 100, causing the second end 1364C of innertube 1358C to come into contact with the fingers formed on second end1363C of outer tube 1356C. Second end 1364C of inner tube 1358Cstraightens and/or spreads out the fingers formed on second end 1363C ofouter tube 1356C until the fingers grab onto or abut against the innerdiameter of stent 100 as shown in FIG. 13D. In one embodiment, thedeployed fingers may slightly expand the inner diameter of stent 100 toincrease the friction between stent 100 and stent suspension means 1328Cto minimize undesired movement of stent 100.

FIGS. 14A-14B illustrate another embodiment of a stent suspension means1428 includes a header or carousel 1436, a portion of which is shown inthe figure, and a mandrel 1450 for holding a stent 100 in place duringthe capillary filling procedure described with reference to FIGS. 4A-7.Although only one mandrel 1450 is shown, it will be understood by one ofordinary skill in the art that a plurality of mandrels may be coupled orattached to header or carousel 1436 for accommodating a plurality ofstents 100. Header or carousel 1436 is a generally flat sheet-likecomponent having at least one hole or passageway 1437 formed therethrough to allow for passage of a portion of mandrel 1450. Mandrel 1450includes two concentric tubes or shafts that extend through passageway14374 of header or carousel 1436, a retractable outer tube 1466 and aninner tube 1458 slidably mounted to extend through a lumen 1457 definedby outer tube 1466. Inner tube 1458 may be a Nitinol tube, and a secondend 1463 of inner tube 1458 includes a plurality of self-expandingfingers, similar to a collet. Outer tube 1466 has an outer diameter lessthan the inner diameter of stent 100. In operation, stent 100 ispositioned over outer tube 1466, which radially constrains the fingersformed on second end 1463 of mandrel 1450 as shown in FIG. 14A. Outertube 1466 may be moved in an “upward” direction toward header orcarousel 1436, as indicated by directional arrow 1441, away from stent100, to expose the fingers formed on second end 1463 of mandrel 1450,causing the fingers formed on second end 1463 of mandrel 1450 toself-expand and radially deploy until the fingers grab onto or abutagainst the inner diameter of stent 100 as shown in FIG. 14B. In oneembodiment, the deployed fingers may slightly expand the inner diameterof stent 100 to increase the friction between stent 100 and stentsuspension means 1428 to minimize undesired movement of stent 100. Whenit is desired to retract or radially constrain the fingers formed onsecond end 1463 of mandrel 1450, outer tube 1466 is moved in a downwardsdirection to resume the configuration shown in FIG. 14A.

FIGS. 15A-15B illustrate another embodiment of a stent suspension means1528 includes a header or carousel 1536, a portion of which is shown inthe figure, and a mandrel 1550 for holding a stent 100 in place duringthe capillary filling procedure described with reference to FIGS. 4A-7.Although only one mandrel 1550 is shown, it will be understood by one ofordinary skill in the art that a plurality of mandrels may be coupled orattached to header or carousel 1536 for accommodating a plurality ofstents 100. Header or carousel 1536 is a generally flat sheet-likecomponent having at least one hole or passageway 1537 formed therethrough. Mandrel 1550 is a hollow shaft or tube having a hole 1517formed in a sidewall thereof, and a first end 1562 of mandrel 1550 iscoupled to header or carousel 1536. A Nitinol wire 1568 having a firstend 1569A and a second end 1569B extends through passageway 1537 ofheader 1536, through the lumen of mandrel 1550, exits out of hole 1517formed in the mandrel, and tightly wraps or winds around the exteriorsurface of mandrel 1550 as shown in FIG. 15A. Second end 1569B iscoupled to a second end 1563 of mandrel 1550. In operation, stent 100 ispositioned over mandrel 1550. Once stent 100 is in position as desired,tension on wire 1568 is released, causing helical Nitinol wire 1568 toself-expand and radially deploy to its shape set configuration in whichthe helical windings thereof grab onto or abut against the innerdiameter of stent 100 as shown in FIG. 15B. Wire 1568 may be pulled backto its original position shown in FIG. 15A by retracting the wire backinto the lumen of mandrel 1550, thereby reducing the diameter of thehelical windings of wire 1568. In one embodiment, the deployed helicalwindings of helical Nitinol wire 1568 may slightly expand the innerdiameter of stent 100 to increase the friction between stent 100 andstent suspension means 1528 to minimize undesired movement of stent 100.

FIG. 16 illustrates another embodiment of a stent suspension means 1628includes a header or carousel 1636, a portion of which is shown in thefigure, and an elongated tubular component 1672 for holding a stent 100in place during the capillary filling procedure described with referenceto FIGS. 4A-7. Although only one tubular component 1672 is shown, itwill be understood by one of ordinary skill in the art that a pluralityof tubular components may be coupled to header or carousel 1636 foraccommodating a plurality of stents 100. Header or carousel 1636 is agenerally flat sheet-like component. A lumen or passageway 1674 oftubular component 1672 is slightly greater than the outer diameter ofstent 100. A first open end 1671 of tubular component 1672 is coupled orattached to header or carousel 1636, and a second open end 1673 oftubular component 1672 is positioned adjacent or proximate to a wickingmeans 1630. Lumen 1674 of tubular component 1672 is in fluidcommunication with a vacuum source 1670. In operation, stent 100 iswithin the lumen of tubular component 1672, and vacuum source 1670 iscontrolled to lower or raise the stent towards or away from wickingmeans 1630 as desired. For example, after stent 100 is filled, suctionmay be applied from vacuum source 1670 in order to retract stent 100away from wicking means 1630. In one embodiment, a cylindrical plug 1675may be positioned within the inner diameter of stent 100 to minimize airpassage through stent 100 when vacuum source 1670 is used to control thelongitudinal position of the stent within tubular component 1672.

FIG. 17 illustrates another embodiment of a stent suspension means 1728that includes a header or carousel 1736, a portion of which is shown inthe figure, and an inflatable balloon 1776 for holding a stent 100 inplace during the capillary filling procedure described with reference toFIGS. 4A-7. Although only one balloon 1776 is shown, it will beunderstood by one of ordinary skill in the art that a plurality ofballoons may be coupled to header or carousel 1736 for accommodating aplurality of stents 100. Header or carousel 1736 is a generally flatsheet-like component and a first end 1777 of balloon 1776 is coupled orattached to header or carousel 1736. Balloon 1776 may be a cylindricalor tubular shaped balloon, and an interior 1779 of balloon 1776 is influid communication with an inflation source 1778. Prior to inflation,balloon 1776 has an outer diameter that fits within stent 100. Oncestent 100 is in position as desired, balloon 1776 is inflated viainflation source 1778. Balloon 1776 inflates or expands until itsexterior surface abuts against or is in opposition with the innerdiameter of stent 100 as shown in phantom in FIG. 17. The inflatedballoon 1776 thus grabs onto the inner diameter of stent 100, and in oneembodiment, may slightly expand the inner diameter of stent 100 toincrease friction between stent 100 and stent suspension means 1728 tominimize undesired movement of stent 100. Exemplary materials forballoon 1776 include but are not limited to Polyethylene terephthalate(PET), polyethylene (PE), nylon, nylon blends, polyurethanes,polyesters, Hytrel, PEBA resins, and PEBAX.

FIGS. 18A-18B illustrate another embodiment of a stent suspension means1828 that includes a header or carousel 1836, a portion of which isshown in the figure, and a mandrel 1850 for holding a stent 100 in placeduring the capillary filling procedure described with reference to FIGS.4A-7. Although only one mandrel 1850 is shown, it will be understood byone of ordinary skill in the art that a plurality of mandrels may becoupled to header or carousel 1836 for accommodating a plurality ofstents 100. Header or carousel 1836 is a generally flat sheet-likecomponent having at least one slot or passageway 1837 formed therethrough to allow for passage of a portion of mandrel 1850. Mandrel 1850includes two adjacent pins or shafts, a first stationary pin 1880coupled to header or carousel 1836 and a second movable pin 1881 whichextends through slot 1837 of header or carousel 1836. Second movable pin1881 may be laterally shifted or moved to selectively retain stent 100.More particularly, second movable pin 1881 is mounted in a block 1821above the header carousel 1836 with a compression spring 1819 extendingbetween the block and the header. Compression spring 1819 provides aforce that tends to move the second pin 1881 away from the stationarypin 1880, as shown in FIG. 18B. In operation, a force 1841 is externallyapplied, i.e., applied by an operator pressing on block 1821, tocompress spring 1819 and thereby shift or move second movable pin 1881within slot 1837 so that it is relatively close to stationary pin 1880as shown in FIG. 18A. Stent 100 is then placed over both stationary pin1880 and movable pin 1881, with the first stationary pin 1880 in contactwith the inner surface or diameter of stent 100. Once stent 100 is inposition as desired, force 1841 is removed and spring 1819 resumes itsnatural configuration that laterally moves second pin 1881 away fromstationary pint 1880 as shown in FIG. 18B. When moved apart fromstationary pin 1880, movable pin 1881 comes into contact with the innersurface or diameter of stent 100 and collectively pins 1880, 1881 abutagainst the inner diameter of stent 100 in an interference or frictionfit. Pins 1880, 1881 contact the inner diameter of stent 100 at opposinglocations.

FIGS. 18C-18D illustrate another embodiment of a stent suspension means1828C that includes a header or carousel 1836C, a portion of which isshown in the figure, and a mandrel 1850C for holding a stent 100 inplace during the capillary filling procedure described with reference toFIGS. 4A-7. Although only one mandrel 1850C is shown, it will beunderstood by one of ordinary skill in the art that a plurality ofmandrels may be coupled to header or carousel 1836 for accommodating aplurality of stents 100. Header or carousel 1836C is a generally flatsheet-like component having at least one slot or passageway 1837C formedthere through to allow for passage of a portion of mandrel 1850C.Mandrel 1850C includes two adjacent pins or shafts, a first stationarypin 1880C coupled to header or carousel 1836C and a second movable pin1881C which extends through slot 1837C of header or carousel 1836C.Second movable pin 1881C may be laterally shifted or moved toselectively retain stent 100. More particularly, second movable pin1881C is mounted in a block 1821C above the header carousel 1836C with acompression spring 1819C extending between the block and the header.Compression spring 1819C provides a force that tends to move the secondpin 1881C toward the stationary pin 1880C, as shown in FIG. 18D. Inoperation, a force 1841C is externally applied, i.e., applied by anoperator pressing on block 1821C, to compress spring 1819C and therebyshift or move second movable pin 1881C within slot 1837C so that it isrelatively spaced apart from stationary pin 1880C as shown in FIG. 18C.Stent 100 is then placed between stationary pin 1880C and movable pin1881, with the first stationary pin 1880C in contact with the innersurface or diameter of stent 100. Once stent 100 is in position asdesired, force 1841C is removed and spring 1819C resumes its naturalconfiguration that laterally moves second pin 1881C toward stationarypint 1880C as shown in FIG. 18D. When moved towards stationary pin1880C, movable pin 1881C comes into contact with the an outer surface ordiameter of stent 100 such that a sidewall of stent 100 is effectivelysandwiched or captured between pins 1880C, 1881C.

FIGS. 19A-19D illustrate another embodiment of a stent suspension means1928 that includes a header or carousel 1936, a portion of which isshown in the figure, and a mandrel 1950 for holding a stent 100 in placeduring the capillary filling procedure described with reference to FIGS.4A-7. Although only one mandrel 1950 is shown, it will be understood byone of ordinary skill in the art that a plurality of mandrels may becoupled to header or carousel 1936 for accommodating a plurality ofstents 100. Header or carousel 1936 is a generally flat sheet-likecomponent having at least one slot or passageway 1937 formed therethrough to allow for passage of a portion of mandrel 1950 and a collet1982. Collet 1982 has a tapered or frustoconical outer surface and alumen or hole 1925 extending there through, which is sized slightlylarger than an outer diameter of stent 100. Multiple cuts 1923 areformed at one end of collet, in the sidewall thereof, to form jaws1982A, 1982B, 1983C. Mandrel 1950, having an outer diameter slightlysmaller than the inner diameter of stent 100, extends through lumen 1925of collet 1982. In operation, stent 100 is placed over mandrel 1950 andwithin collet 1982 as shown in FIGS. 19A-19B. Cuts 1923 in collet 1982allow adjacent jaws of the collet to spread apart. Once stent 100 is inposition as desired, collet 1982 may be moved in an “upward” directiontoward header or carousel 1936, as indicated by directional arrow 1441,away from stent 100, until the outer surface of the collet contacts theedge of passageway 1937 of header 1936. When the outer diameter ofcollet 1982 is greater than the diameter of passageway 1937, passageway1937 applies an inward radial force onto the collet and squeezes ormoves jaws 1982A, 1982B, 1983C together as shown in FIGS. 19C-19D. Aninner diameter of lumen 1925 of collet 1982 is reduced to effectivelyclamp or capture stent 100 between the inner surface of collet 1982 andthe exterior surface of mandrel 1950.

FIG. 20 illustrates another embodiment of a stent suspension means 2028that includes a header or carousel 2036, a portion of which is shown inthe figure, and a mandrel 2050 for holding a stent 100 in place duringthe capillary filling procedure described with reference to FIGS. 4A-7.Although only one mandrel 2050 is shown, it will be understood by one ofordinary skill in the art that a plurality of mandrels may be coupled toheader or carousel 2036 for accommodating a plurality of stents 100.Header or carousel 2036 is a generally flat sheet-like component and afirst end 2062 of mandrel 2050 is coupled to header or carousel 2036.Mandrel 2050 includes a wavy or bumpy exterior surface adjacent to atleast a second end 2063. The wavy or bumpy exterior surface of mandrel2050 is formed via circumferential ribs or bands 2083 having anincreased outer diameter relative to the remainder of mandrel 2050. Thewavy or bumpy exterior surface of mandrel 2050 abuts against the innerdiameter of stent 100 in an interference or friction fit. Mandrel 2050may be formed from 3 series stainless steel, or other material that isnot prone to oxidation or corrosion, and is not dissolvable andunaffected by harsh chemicals. In another embodiment (not shown),mandrel 2050 may have a straight exterior surface that abuts against theinner diameter of stent 100 in an interference or friction fit and thetip of the slip-fit mandrel may include a chamfer, a taper, or may besubstantially flat for an improved fit with the stent. In yet anotherembodiment (not shown), rather than a tubular shaft or rod as a mandrel,the stent suspension means may consist of one or more springs or coiledwires that are offset from each other and collectively form a tubularmandrel. The springs or coiled wires that make up a tubular mandrel abutagainst the inner diameter of stent 100 in an interference or frictionfit.

FIGS. 21-21A illustrate another embodiment of a stent suspension means2128 that includes a header or carousel 2136, a portion of which isshown in the figure, and a mandrel 2150 for holding a stent 100 in placeduring the capillary filling procedure described with reference to FIGS.4A-7. FIG. 21A is a top view of FIG. 21 with header or carousel 2136removed. Although only one mandrel 2150 is shown, it will be understoodby one of ordinary skill in the art that a plurality of mandrels may becoupled to header or carousel 2136 for accommodating a plurality ofstents 100. Header or carousel 2136 is a generally flat sheet-likecomponent and a first end portion 2162 of mandrel 2150 is coupled toheader or carousel 2136. First end portion 2162 of mandrel 2150 has asmaller outer diameter than a second end portion 2163 of mandrel 2150.The outer diameter of second end portion 2163 of mandrel 2150 abutsagainst the inner diameter of stent 100 in an interference or frictionfit. To position stent 100 over mandrel 2150, stent 100 is slid upmandrel 2150 until end 105 of stent 100 is past wider second end portion2163 of mandrel 2150 and is positioned over narrower first end portion2162 of mandrel 2150. A stationary cantilevered spring leaf or arm 2184extends adjacent to first end portion 2162 of mandrel 2150 and contactsand abuts against end 105 of stent 100. When stent 100 is lowered intowicking component 430 within second chamber 424, the stent mayexperience an upward force due to the interaction of the stent with thewicking component 430 that may cause the stent to unintentionally slipup mandrel 2150. Spring arm 2184 counters any unintentional upwardforces that result due to the interaction of the stent with the wickingcomponent 430 by exerting a downward force onto stent 100 if spring arm2184 is deflected from its neutral position shown in FIG. 21. Spring arm2184 thus acts to press stent 100 into the wicking component for moreuniform loading during the filling process when a plurality of stentsare present.

FIGS. 22A-22C illustrate another embodiment of a stent suspension means2228 that includes a header or carousel 2236, a portion of which isshown in the figure, and a mandrel 2250 for holding a stent 100 in placeduring the capillary filling procedure described with reference to FIGS.4A-7. FIG. 22C is a sectional view taken along line C-C of FIG. 22B.Although only one mandrel 2250 is shown, it will be understood by one ofordinary skill in the art that a plurality of mandrels may be coupled toheader or carousel 2236 for accommodating a plurality of stents 100.Header or carousel 2236 is a generally flat sheet-like component and afirst end 2262 of mandrel 2250 is coupled to header or carousel 2236. Inoperation, stent 100 is placed over mandrel 2250 as shown in FIG. 22A.Once stent 100 is in position as desired, a spring-loaded, movable arm2285 pushes stent 100 against mandrel 2250 as shown in FIGS. 22B and 22Cto effectively sandwich or capture stent 100 between arm 2285 and theexterior surface of mandrel 2250. Arm 2285 rotates or moves via a spring2286 and a pivot 2287.

Means for Wicking Fluid Drug Formulation

FIGS. 23-33 illustrate several embodiments of wicking means 430, whichis in contact with fluid drug formulation 432 to control transfer of thefluid drug formulation 432 into lumen 103 of hollow wire 102 during thecapillary filling procedure as described in FIGS. 4A-7. “Wicking means”as used herein refers to a medium or component that acts or functions tomove or convey, or acts or functions to assist in the movement of, thefluid drug formulation 432 by capillary action from within second orlower chamber 424 into lumen 103 of hollow wire 102. In addition tocontrolling transfer of the fluid drug formulation, in some embodimentshereof, wicking means 430 also removes excess fluid drug formulationfrom the exterior surfaces of hollow wire 102 of stent 100 when stent100 is retracted out of the wicking means. When wicking means 430performs this excess removal function, an additional processing orcleaning step is not required to make stents 100 free or substantiallyfree of drug residue on the exterior surfaces of hollow wire 102.Wicking means 430 preferably has several characteristics or properties,including that is does not degrade or add contaminants into fluid drugformulation 432, that it is inert in fluid drug formulation 432, that itdoes not cause a phase separation within fluid drug formulation 432, andthat it is usable and/or stable for several days or weeks.

As previously mentioned, in one embodiment wicking means 430 is anopen-celled polyurethane sponge. Several characteristics or propertiesmay be varied to improve the sponge's effectiveness to further reducefill weight variability, including the polymer material's chemicalstructure, the hydrophilicity of the sponge, the pore size of thesponge, the density of the sponge, the compression modulus of thesponge, and/or the shape or dimensions of the sponge. For example,hydrophilicity and pore size have a direct correlation with capillaryaction and therefore fluid affinity. Thus, optimization of theseproperties allows the sponge to better clean the exterior surfaces ofhollow wire 102 of stent 100. In addition, the compression modulus ofthe sponge allows for a controlled amount of the stent to come intocontact with the wicking means. An optimized amount of deformationpermits the sponge to come into contact with side holes 104 of stent 100while limiting the amount of exterior surface of hollow wire 102 ofstent 100 that comes into contact with the fluid drug formulation.

As an alternative to a sponge wicking means, the wicking means may be anintermediate surface or component between the stents and the fluid drugformulation 432 that makes contact with fluid drug formulation 432 tocontrol transfer of the fluid drug formulation 432 into lumen 103 ofhollow wire 102 during the capillary filling procedure as described inFIGS. 4A-7. For illustrative purposes, stents 100 are represented asstraight tubular structures in FIGS. 23-33 although it will beunderstood by one of ordinary skill in the art that stents 100 are ahollow wire shaped into a desired stent pattern as discussed withreference to FIG. 1. For example, FIG. 23 illustrates a portion of loweror second chamber 424 having a portion of a stent 100 lowered to contacta wicking means 2330. Wicking means 2330 is a deformable membrane orsheet that is held over a layer of fluid drug formulation 432 heldwithin a container 2327 second chamber 424. In one embodiment, wickingmeans 2330 is a continuous filament polyester fiber sheet of material,or a purity wipe. The position or configuration of wicking means 2330 iscontrolled via two concentric tubes, a first or outer stationary tube2388A and a second or inner movable tube 2388B. Tubes 2388A, 2388B maybe cylindrical or rectangular in cross-section. Wicking means 2330extends or drapes over a top of outer stationary tube 2388A and is heldin place over outer stationary tube 2388A via an O-ring 2329 formed ofan inert substance such as Teflon. In another embodiment, wicking means2330 may be held in place over outer stationary tube 2388A via a clamp.In operation, wicking means 2330 is draped over outer stationary tube2388A such that a center of the wicking means sages and contacts fluiddrug formulation 432 held within container 2327 as shown in FIG. 23A.Wicking means 2330 thus becomes wetted with fluid drug formulation 432in a first configuration such that when end 107 of stent 100 is placedinto contact with wicking means 2330, fluid drug formulation 432 fillsor is wicked up into lumen 103 of hollow wire 102 via capillary action.When filling is complete, stent 100 is raised in conjunction with innermovable tube 2388B. Inner movable tube 2388B is raised via an appliedelectromotive force via an EMF source, and pushes wicking means 2330upwards into a second configuration in which the deformable sheet is notin contact with fluid drug formulation 432 held within container 2327 asshown in FIG. 23B. The deformable sheet or membrane of wicking means2330 becomes taut and allows excess fluid drug formulation on exteriorsurfaces of hollow wire 102 of stent 100 to drain from the stent ontothe wicking means. Once the excess fluid drug formulation 432 hasdrained, the electromotive force is removed and inner movable tube 2388Bis lowered to the original position of FIG. 23A.

FIG. 24 is another embodiment of the wicking means as an intermediatesurface or component that is in contact with fluid drug formulation 432to control transfer of the fluid drug formulation 432 into lumen 103 ofhollow wire 102 during the capillary filling procedure as described inFIGS. 4A-7. FIG. 24 illustrates a portion of lower or second chamber 424having a portion of a stent 100 lowered to contact a wicking means 2430.Wicking means 2430 is mesh material positioned within a layer of fluiddrug formulation 432 contained within second chamber 424. When end 107of stent 100 is placed into contact with wicking means 2430, the meshmaterial deforms or buckles in order to connect and allow contactbetween stent 100 and the layer of fluid drug formulation 432. Afterstents 100 have been filled, stents 100 are retracted from contact withwicking means 2430. During retraction of stents 100, the mesh materialof wicking means 2430 returns to its original shape and pulls or removesexcess fluid drug formulation from the exterior surfaces of stents 100.Exemplary materials for the mesh material of wicking means 2430 includebut are not limited to nylon, polyester, polypropylene, or rubber.

FIG. 25 is another embodiment of the wicking means as an intermediatesurface or component that is in contact with fluid drug formulation 432to control transfer of the fluid drug formulation 432 into lumen 103 ofhollow wire 102 during the capillary filling procedure as described inFIGS. 4A-7. FIG. 25 illustrates a portion of second chamber 424 having aportion of a stent 100 lowered to contact a wicking means 2530. Wickingmeans 2530 is flocked or textured material positioned within a layer offluid drug formulation 432 contained within second chamber 424. Theflocked or textured sheet of material may be VELCRO, cotton, cellulose,polymer foam, porous polymer blocks, or polymer fibers, and/orartificial grass. When end 107 of stent 100 is placed into contact withwicking means 2530, the textured material deforms or buckles in order toconnect and allow contact between stent 100 and the layer of fluid drugformulation 432. After stents 100 have been filled, stents 100 areretracted from contacting wicking means 2530. During retraction ofstents 100, the textured material of wicking means 2530 returns to itsoriginal shape and pulls or removes excess fluid drug formulation fromthe exterior surfaces of hollow wires 102 of stents 100.

FIG. 26 is another embodiment of the wicking means as an intermediatesurface or component that is in contact with fluid drug formulation 432to control transfer of the fluid drug formulation 432 into lumen 103 ofhollow wire 102 during the capillary filling procedure as described inFIGS. 4A-7. FIG. 26 illustrates a portion of second chamber 424 having aportion of a stent 100 lowered through a wicking means 2630. Wickingmeans 2630 is a layer of PEG (polyethylene glycol) gel or an immiscibleliquid that, when poured into second chamber 424, will separate from andform a top layer on the fluid drug formulation 432. End 107 of stent 100is placed through wicking means 2630 until the stents 100 are in contactwith the layer of fluid drug formulation 432. After stents 100 have beenfilled, stents 100 are retracted through wicking means 2630. Duringretraction of stents 100, the cellulose, PEG gel, or immiscible liquidmay pull or remove excess fluid drug formulation from the exteriorsurfaces of stents 100.

FIGS. 27A-27B illustrates another embodiment of the wicking means thatincludes an intermediate surface or component that is in contact withfluid drug formulation 432 to control transfer of the fluid drugformulation 432 into lumen 103 of hollow wire 102 during the capillaryfilling procedure as described in FIGS. 4A-7. FIGS. 27A-27B illustrate aportion of second chamber 424 having a portion of a stent 100 lowered tocontact a wicking means 2730. Wicking means 2730 is a plurality ofhypotubes or cylindrical microchannels within the layer of fluid drugformulation 432 contained within second chamber 424. The hypotubes areformed out of material that changes orientation when a magnetic orelectric field is applied thereto. Stent 100 is placed into thehypotubes of wicking means 2730 until end 107 stent 100 contacts thelayer of fluid drug formulation 432. The individual size of thehypotubes, as well as the height of the layer of hypotubes, may varyaccording to application. During the filling steps, the hypotubes ofwicking means 2730 have a first or vertical orientation shown in FIG.27A which allows fluid drug formulation 432 to pass through the hypotubelumens via capillary action. When fluid drug formulation 432 travels upthe hypotubes of wicking means 2730, fluid drug formulation 432 comesinto contact with end 107 of stent 100, thereby allowing the lumen 103of hollow wire 102 of stent 100 to fill via capillary action. Only theopen bottoms of the hypotubes are required to be submersed in the fluiddrug formulation in order to fill the hypotubes via capillary action.After stents 100 have been filled, an electric or magnetic field isapplied to move the hypotubes of wicking means 2730 to a second orhorizontal orientation. In the horizontal orientation shown in FIG. 27B,fluid drug formulation 432 does not contact or interact with stent 100so filling of the stent via capillary action is stopped. Changing theorientation of the hypotubes of wicking means 2730 changes the fluidtransfer properties between stent 100 and fluid drug formulation 432. Intheir vertical orientation, hypotubes readily transfer fluid drugformulation 432 to stent 100 and in their horizontal orientation,capillary action is stopped and fluid affinity is modified to make iteasier to clean the exterior surfaces of hollow wire 102 of stent 100.

FIG. 28 is another embodiment of the wicking means as an intermediatesurface or component that is in contact with fluid drug formulation 432to control transfer of the fluid drug formulation 432 into lumen 103 ofhollow wire 102 during the capillary filling procedure as described inFIGS. 4A-7. FIG. 28 illustrates a portion of lower or second chamber 424having a portion of a stent 100 lowered to contact a wicking means 2830.Wicking means 2830 is a cellulose column positioned within and extendingpast or beyond a layer of fluid drug formulation 432 contained withinsecond chamber 424. End 107 of stent 100 is placed into contact with aside surface of wicking means 2830, which acts as a bridge or conduitbetween stent 100 and fluid drug formulation 432 to transfer the fluiddrug formulation to stent 100. End 107 of stent 100 may alternatively beplaced into contact with a top surface of wicking means 2830. Thecellulose column minimizes the contact area between stents 100 and fluiddrug formulation 432 to control surface energy properties during thefilling procedure. As described in more detail here with respect toembodiments in which the stent directly contacts the fluid drugformulation, the surface energy properties of the fluid drug formulationmust be controlled in order for the fluid drug formulation to have thegreatest affinity for lumen 103 of hollow wire 102 rather than on theexterior surfaces of hollow wire 102 so that the maximum amount ofexterior surfaces are kept clean, or substantially free of fluid drugformulation 432, during the filling process.

Similar to FIG. 28, FIG. 29 is another embodiment of the wicking meansas an intermediate surface or component that is in contact with fluiddrug formulation 432 to control transfer of the fluid drug formulation432 into lumen 103 of hollow wire 102 during the capillary fillingprocedure as described in FIGS. 4A-7. FIG. 29 illustrates a portion oflower or second chamber 424 having a portion of a stent 100 lowered tocontact a wicking means 2930. Wicking means 2930 is a fiber/filament ora plurality of woven or parallel fibers/filaments positioned within andextending past or beyond a layer of fluid drug formulation 432 containedwithin second chamber 424. End 107 of stent 100 is placed into contactwith a top surface of wicking means 2930 such that wicking means 2930 isin direct contact with an opening or hole 104 formed within wire 102.Wicking means 2930 transfers fluid drug formulation 432 to stent 100 andminimizes the contact area between stents 100 and fluid drug formulation432 to control surface energy properties during the filling procedure.In another embodiment, wicking means 2930 is a plug of cotton or similarfibrous material.

In FIGS. 28 and 29, the cellulose column or fiber(s) are positionedwithin and extending past or beyond a layer of fluid drug formulation432 contained within second chamber 424. Alternatively, as shown in FIG.30, a wicking means 3030 may extend from end 107 of stent 100 and bedipped or lowered into a layer of fluid drug formulation 432. FIG. 30illustrates a portion of lower or second chamber 424 having a portion ofa stent 100 lowered to contact wicking means 3030. Wicking means 3030may be a cellulose extension, a fiber/filament, a plurality of woven orparallel fibers/filaments, or a plug of cotton. Wicking means 3030 iscoupled to end 107 of stent 100, and stent 100 is lowered within secondchamber 424 until a bottom surface of wicking means 3030 is in contactwith fluid drug formulation 432. Wicking means 3030 transfers fluid drugformulation 432 to stent 100 and minimizes the contact area betweenstent 100 and fluid drug formulation 432 to control surface energyproperties during the filling procedure.

FIGS. 31A-31B illustrate another embodiment of the wicking means inwhich an intermediate surface or component that is in contact with fluiddrug formulation 432 to control transfer of the fluid drug formulation432 into lumen 103 of hollow wire 102 during the capillary fillingprocedure as described in FIGS. 4A-7. FIGS. 31A-31B illustrate a portionof lower or second chamber 424 having a portion of a stent 100 loweredto contact a wicking means 3130A, 3130B, respectively. Wicking means3130A is a sheet or generally flat solid/impervious substrate in contactwith a heating element HE, while wicking means 3130B is a porous oropen-celled substrate in contact with a heating element HE. To fillstent 100 via capillary action in FIG. 31A, fluid drug formulation 432is placed on the top surface of impervious wicking means 3130A. Fluiddrug formulation 432 spreads out over the top surface of wicking means3130A, thereby extending to or reaching stent 100 which is also placedon or adjacent to the top surface of wicking means 3130A. To fill stent100 via capillary action in FIG. 31B, stent 100 is brought into contactwith the top surface of porous wicking means 3130B, which is in contactwith fluid drug formulation 432 and conveys the fluid drug formulationto the stent. When filling is complete, wicking means 3130A, 3130B areheated via the heating element to alter the surface tension of thewicking means. When wicking means 3130A, 3130B are heated, the surfacetension forces between fluid drug formulation 432 and stent 100 areweakened and the fluid drug formulation is prevented from adhering tothe interface between wicking means 3130A, 3130B and stent 100. Changesof the temperature of wicking means 3130A, 3130B changes surfacetension/affinity properties, and thereby controls transfer of the fluiddrug formulation 432 into lumen 103 of hollow wire 102 during thecapillary filling procedure.

FIGS. 32A-32B illustrate another embodiment of the wicking means inwhich an intermediate surface or component that is in contact with fluiddrug formulation 432 to control transfer of the fluid drug formulation432 into lumen 103 of hollow wire 102 during the capillary fillingprocedure as described in FIGS. 4A-7. FIGS. 32A-32B illustrate a portionof lower or second chamber 424 having a portion of a stent 100 loweredto contact a wicking means 3230A, 3230B, respectively. Wicking means3230A is a sheet or generally flat solid/impervious substrate in contactwith a voltage source (not shown), while wicking means 3230B is a porousor open-celled substrate in contact with a voltage (not shown). Wickingmeans 3230A, 3230B are formed from a polymer material that switchesbetween hydrophilic and hydrophobic based upon applied voltage. To fillstent 100 via capillary action in FIG. 32A, fluid drug formulation 432is placed on the top surface of impervious wicking means 3230A. Fluiddrug formulation 432 spreads out over the top surface of wicking means3230A, thereby extending to or reaching stent 100 which is also placedon or adjacent to the top surface of wicking means 3230A. To fill stent100 via capillary action in FIG. 32B, stent 100 is brought into contactwith the top surface of porous wicking means 3230B, which is in contactwith fluid drug formulation 432 and conveys the fluid drug formulationto the stent. During the filling step, wicking means 3230A, 3230B ishydrophobic to allow fluid drug formulation 432 to fill stent 100 viacapillary action. When filling is complete, a voltage or potential isapplied to wicking means 3230A, 3230B via the voltage source to changethe wicking means to hydrophilic. When the wicking means becomeshydrophilic, the surface tension forces between fluid drug formulation432 and stent 100 is weakened and the fluid drug formulation isprevented from adhering to the interface between wicking means 3230A,3230B and stent 100. Suitable polymers for wicking means 3230A, 3230Bare described in “Electrically Controlled Hydrophobicity in a SurfaceModified Nanoporous Carbon” by Kim et al. (2011) and “Electrowetting ofWater and Aqueous Solutions on Poly(ethylene Terephthalate) InsulatingFilms” by Vallet et al. (1996), each of which is herein incorporated byreference in its entirety.

FIG. 33 is another embodiment of the wicking means as an intermediatesurface or component that is in contact with fluid drug formulation 432to control transfer of the fluid drug formulation 432 into lumen 103 ofhollow wire 102 during the capillary filling procedure as described inFIGS. 4A-7. FIG. 33 illustrates a portion of lower or second chamber 424having a portion of a stent 100 lowered to contact a wicking means 3330.Wicking means 3330 is a porous or open-celled substrate. In anembodiment, wicking means 3330 includes a top layer or polyurethanesheet that has been welded to a sheet of open celled polyethylene foam.A top surface or portion of wicking means 3330 is more hydrophilic thana center or middle portion of wicking means 3330. Wicking means 3330 isin contact with fluid drug formulation 432 and conveys the fluid drugformulation to the stent. To initiate filling, stent 100 is pressed intothe less hydrophilic center of wicking means 3330. Since the centerportion of wicking means 3330 is less hydrophilic, fluid drugformulation 432 is permitted to fill stent 100 via capillary action.When filling is complete, stent 100 is retracted out of wicking means3330 and as the stent passes through the top portion, any excess fluiddrug formulation 432 which is on an exterior surface of the hollow wireis attracted to the more hydrophilic top portion of wicking means 3330.Thus, during retraction of stents 100, the more hydrophilic top portionof wicking means 3370 may pull or remove excess fluid drug formulationfrom the exterior surfaces of hollow wires 102 of stents 100.

FIGS. 34-38B illustrate various wicking means embodiments in which thewicking means that minimize the contact area between stent 100 and fluiddrug formulation 432 in order to assist in the movement of fluid drugformulation 432 into lumen 103 of hollow wire 102. More particularly, inthe embodiments of FIGS. 34-38B, a portion of each stent 100 directlycontacts fluid drug formulation 432 but a wicking means is utilized inorder to minimize the contact area there between. For illustrativepurposes, stents 100 are represented as straight tubular structures inFIGS. 34-38B although it will be understood by one of ordinary skill inthe art that stents 100 are a hollow wire shaped into a desired stentpattern as described with reference to FIG. 1. When stents 100 contactfluid drug formulation 432 directly, the surface energy properties ofthe fluid drug formulation are preferably controlled in order toaccurately and predictably fill lumen 103 of hollow wire 102. Withoutmodification of the surface energy properties, the fluid drugformulation may travel up the lumen or central blood flow passageway 113of stent 100 (see FIG. 1A) and stick to the inner surface or diameter ofthe stent. It is preferable for fluid drug formulation 432 to have thegreatest affinity for lumen 103 of hollow wire 102 rather than on theexterior surfaces of hollow wire 102 so that the maximum amount ofexterior surfaces are kept clean, or substantially free of fluid drugformulation 432, during the filling process. One way to decrease thesurface tension of fluid drug formulation 432 is to utilize a wickingmeans that minimizes the contact area between stent 100 and fluid drugformulation 432.

More particularly, FIG. 34 is an embodiment hereof in which a wickingmeans 3430 is utilized to reduce the amount of fluid drug formulation432 exposed to stent 100. FIG. 34 illustrates a portion of lower orsecond chamber 424 having a portion of a stent 100 lowered to contact(not shown) a wicking means 3430. Although only one stent 100 is shown,it will be understood by one of ordinary skill in the art that wickingmeans 3430 may accommodate a plurality of stents 100. Wicking means 3430includes a wire loop 3490 coupled to a wire handle 3491. Stent 100 isplaced into second chamber 424 until end 107 of stent 100 is just abovebut not in contact with the layer of fluid drug formulation 432. Wickingmeans 3430 is lifted out of fluid drug formulation 432 and brought intocontact with end 107 of stent 100. Loop 3490 includes a film of fluiddrug formulation 432 similar to a bubble blower loop having a film ofbubble solution after the blower loop is lifted out of bubble solution.When brought into contact with the film of fluid drug formulation 432held within loop 3490, stent 100 breaks the film and fluid drugformulation 432 is transferred to stent 100 via capillary action.Wicking means 3430 transfers a smaller amount of fluid drug formulation432 to stent 100 and thereby reduces the contact area between stents 100and fluid drug formulation 432 to control surface energy propertiesduring the filling procedure. Wire loop 3490 may be re-submerged intofluid drug formulation 432 and the filling steps repeated until stent100 is completely filled.

FIG. 35 is another embodiment for minimizing the contact area betweenstent 100 and fluid drug formulation 432. FIG. 35 illustrates a portionof lower or second chamber 424 having a portion of a stent 100 loweredto contact a wicking means 3530. Although only one stent 100 is shown,it will be understood by one of ordinary skill in the art that wickingmeans 3530 may accommodate a plurality of stents 100. Wicking means 3530is a plurality of beads within the layer of fluid drug formulation 432contained within second chamber 424. Stent 100 is placed into a layer ofbeads until end 107 of stent 100 contacts fluid drug formulation 432.The individual size of the beads, as well as the height of the layer ofbeads, may vary according to application. The beads minimize the contactarea between stents 100 and fluid drug formulation 432 to controlsurface energy properties during the filling procedure. After stents 100have been filled, stents 100 are retracted through the beads of wickingmeans 3530. During retraction of stents 100, the beads pull or removeexcess fluid drug formulation from the exterior surfaces of hollow wires102 of stents 100. In FIG. 35, the layer of fluid drug formulation isapproximately the same height as the layer of beads. However, in anotherembodiment (not shown), the layer of beads has a greater height than thelayer of fluid drug formulation such that a layer of “dry” beads extendover the “wet” beads that are submersed in the layer of fluid drugformulation. The layer of “dry” beads provides additional cleaning ofthe exterior surfaces of stents 100 when stents 100 are retracted out ofthe beads. In an embodiment, the beads of wicking means 3430 may bestirred or shifted during the filling and retracting steps of theprocess. For example, a magnetic stir stick (not shown) may be used tostir the beads and ensure that the stents are constantly supplied withfluid drug formulation during the filling step. In another example, apiezoelectric crystal (not shown) may be used to vibrate the beadswithin second chamber 424 to ensure that the stents are constantlysupplied with fluid drug formulation during the filling step.

In one embodiment, the beads of wicking means 3530 may be glass beads.Other suitable materials for the beads of wicking means 3530 includeceramic, steel, aluminum, titanitum, or stainless steel. Optionally, thebeads may be encased in a mesh bag or container (not shown) to ensurethat the beads do not stick to stent 100. In another embodiment, thebeads may be formed out of a magnetic material. If the magnetic beadsstick to stent 100 when stent 100 is retracted out of the wicking means,a magnet (not shown) may be utilized to remove the magnetic beads fromstent 100.

FIGS. 36A-37C illustrate another embodiment for minimizing the contactarea between stent 100 and fluid drug formulation 432. FIG. 36Aillustrates a portion of second chamber 424 having a portion of a stent100 lowered to contact a wicking means 3630, while FIGS. 37B and 37Cillustrate top and side views, respectively, of the wicking means 3630removed from the chamber and devoid of fluid drug formulation forillustrative purposes. Wicking means 3630 is a generally flat solidplate 3692 having a plurality of reservoirs or grooves 3694 formed on atop surface thereof. Grooves 3694 are channels that are etched ontoplate 3692 and function to receive fluid drug formulation. The size andshape of each groove depends upon the size and shape of a stent which isto be placed into contact with the fluid drug formulation within thegroove. Although wicking means 3630 is shown with six grooves 3694 foraccommodating six stents, it will be understood by one of ordinary skillin the art that wicking means 3630 may include a greater or lessernumber of grooves to accommodate the desired number of stents. Plate3692 is shown as rectangular, but may be any shape that fits within andon a bottom surface of chamber 424. In an embodiment, plate 3692 isglass. Plate 3692 is positioned on the bottom surface of chamber 424,and fluid drug formulation 432 is poured into grooves 3694. Stent 100 islowered into second chamber 424 until end 107 of each stent 100 contactsfluid drug formulation 432 contained within a respective groove 3694.Since fluid drug formulation 432 is only held within grooves 3694 ratherthan as a layer on the bottom surface of the chamber, wicking means 3630minimizes the contact area between stents 100 and fluid drug formulation432 to control surface energy properties during the filling procedure.

Similar to the embodiment of FIGS. 36A-36C, FIGS. 37A-37C illustrateanother embodiment for minimizing the contact area between stent 100 andfluid drug formulation 432. FIG. 37A illustrates a portion of secondchamber 424 having a portion of a stent 100 lowered to contact a wickingmeans 3730, while FIGS. 37B and 37C illustrate top and side views,respectively, of the contact area minimize 3730 removed from the chamberand devoid of fluid drug formulation for illustrative purposes. Wickingmeans 3730 is a generally flat solid plate 3792 having a plurality ofholes or fluid passageways 3794 formed there through. Although wickingmeans 3730 is shown with six holes 3794 for accommodating six stents, itwill be understood by one of ordinary skill in the art that wickingmeans 3730 may include a greater or lesser number of holes toaccommodate the desired number of stents. Plate 3792 is shown asrectangular, but may be any shape that fits within and on a bottomsurface of chamber 424. In an embodiment, plate 3792 is stainless steel.Plate 3792 is positioned within chamber 424 on top of a layer of fluiddrug formulation 432. Fluid drug formulation 432 seeps through and fillsholes 3794 of plate 3792 as shown in FIG. 37A. The size and shape ofeach hole depends upon the size and shape of a stent which is to beplaced into contact with the fluid drug formulation disposed within thehole. To initiate fill, plate 3792 is placed on top of a layer of fluiddrug formulation 432 such that fluid drug formulation 432 seeps up intoand fills holes 3794 of plate 3792. Stents 100 are then lowered intosecond chamber 424 until end 107 of each stent 100 contacts the fluiddrug formulation 432 disposed within a respective hole 3794.Alternatively, to initiate fill, stents 100 may first be lowered into aposition slightly above the layer of fluid drug formulation 432, andplate 3792 may subsequently be lowered into fluid drug formulation 432with stents 100 passing through holes 3794 of plate 3792. After theplate is placed on top of the layer of fluid drug formulation 432, thefluid drug formulation 432 will seep up or rise into holes 3794 andcontact ends 107 of stents 100. Since stents 100 only contact arelatively small amount of fluid drug formulation 432 held within holes3794, wicking means 3730 minimizes the contact area between stents 100and fluid drug formulation 432 to control surface energy propertiesduring the filling procedure. After filling is complete, stents 100and/or plate 3792 may be retracted such that stents 100 are no longer incontact with fluid drug formulation 432.

FIGS. 38A-38B illustrate another embodiment for minimizing the contactarea between stent 100 and fluid drug formulation 432. FIG. 38Aillustrates a portion of lower or second chamber 424 having a portion ofa stent 100 lowered to contact (not shown) a wicking means 3830.Although only one stent 100 is shown, it will be understood by one ofordinary skill in the art that wicking means 3830 may accommodate aplurality of stents 100. Wicking means 3830 is a movable plate having anouter diameter or dimension smaller than an inner diameter or dimensionof second chamber 424. Prior to and/or during the filling step, themovable plate of wicking means 3830 is positioned within the layer offluid drug formulation 432, i.e., below the top surface of the layer, asshown in FIG. 38A. To initiate filling, stents 100 are lowered intosecond chamber 424 until end 107 of stent 100 contacts the layer offluid drug formulation 432. When it is desired to slow or stop filling,the movable plate of wicking means 3830 is moved up towards stent 100.The movable plate of wicking means 3830 maybe moved via any suitablemechanical or magnetic means. As the movable plate of wicking means 3830is being moved up, the amount of fluid drug formulation 432 exposed tostent 100 is continually decreased, thereby slowing filling of stent100. When the movable plate is positioned adjacent to end 107 of stent100, above the top surface of the layer of fluid drug formulation 432 asshown in FIG. 38B, stent 100 is no longer in contact with the layer offluid drug formulation 432 and thus stent 100 stops filling.

Although wicking means embodiments described herein may be shown withonly one stent 100, it will be understood by one of ordinary skill inthe art that any wicking means described herein may accommodate aplurality of stents 100.

Embodiments in which Stents Directly Contact Fluid Drug Formulationwithout a Wicking Means

Although the capillary filling procedure described in FIGS. 4A-7utilizes a wicking means 430 that is in contact with drug formulation3932, in another embodiment hereof stent 100 may contact the fluid drugformulation directly without a wicking means. More particularly, FIG. 39is a schematic illustration of an apparatus 3920 for filling lumen 103of a stent 100 with a fluid drug formulation 3932 via capillary actionwithout the use of a wicking means. Similar to apparatus 420, apparatus3920 includes a first or upper chamber 3922 which houses a manifold orstent suspension means 3928 and a reservoir 3931 filled with a liquid orfluid solvent 3933, a second or lower chamber 3924 which houses a fluiddrug formulation 3932 that includes therapeutic substance or drug 112,and a valve 3926 extending between upper chamber 3922 and lower chamber3924. Solvent 3933 within reservoir 3931 is the same solvent as used influid drug formulation 3932. A plurality of stents 100 are loaded ontostent suspension means 3928, which holds them in place during thecapillary filling procedure and may be any stent suspension meansdescribed herein. Prior to the initiation of capillary filling, valve3926 is closed such that first or upper chamber 3922 and second or lowerchamber 3924 are separated and not in fluid communication. A pressuresource 3934 and a heat source 3935 are connected to the interior of theupper chamber 3922. Before placing stents 100 into upper chamber 3922,pressure source 3934 is used to purge any residual solvent vapor fromthe upper chamber. After the purge, stent suspension means 3928 holdingstents 100 are placed into upper chamber 3922 and pressure source 3934is stopped to allow solvent vapor from reservoir 3931 contained solvent3933 to fill upper chamber 3922. When evaporation has stopped orsufficiently slowed, valve 3926 is opened and first or upper chamber3922 and second or lower chamber 3924 are exposed to each other and influid communication. Both chambers 3922, 3924 are then required to reachor near solvent vapor saturation, or at or near the vapor-liquidequilibrium of solvent 3933, such that little to no net evaporation ofthe fluid drug formulation is present. In order to reduce the amount oftime required for upper and lower chambers 3922, 3924 to reach solventvapor saturation, upper chamber 3922 may include a fan 3999 to createconvection across reservoir 3931 containing a supply of solvent 3933. Inaddition, any of the methods described above with respect to FIGS. 4A-7for reducing the amount of time required to reach solvent vaporsaturation may be utilized.

Once both chambers 3922, 3924 are at or near solvent vapor saturation,capillary filling may be initiated by moving stents 100 into contactwith or submersed into fluid drug formulation 3932. Lumen 103 of hollowwire 102 of stent 100 is filled by surface tension driving fluid drugformulation 3932 through the stent lumen, until the entire length oflumen 103 is filled via capillary action forces. When stents 100 contactfluid drug formulation 3932 directly, the surface energy properties ofthe fluid drug formulation are preferably controlled in order toaccurately and predictably fill lumen 103 of hollow wire 102. Asdescribed above with respect to FIGS. 34-38B, without modification ofthe surface energy properties, the fluid drug formulation may travel upthe lumen or central blood flow passageway 113 of stent 100 (see FIG.1A) and stick to the inner surface or diameter of the stent. In oneembodiment, after filling is complete but prior to the retraction orremoval of the stents from fluid drug formulation 3932, heat source 3935may be utilized to raise the temperature of the fluid drug formulationfrom −50 degrees C. to 60 degrees C. in order to decrease the surfacetension thereof.

The stents are filled via capillary action until lumen 103 of hollowwire 102 is filled. During the filling step, chambers 3922, 3924 must bemaintained at or near the vapor-liquid equilibrium of solvent 3933 suchthat evaporation does not precipitate therapeutic substance or drug 112as fluid drug formulation 3932 fills lumen 103 of hollow wire 102 ofstents 100. After lumen 103 is completely filled, stents 100 areretracted or pulled up such that stents 100 are still located withinlower chamber 3924 but ends 107 of stents 100 are no longer in contactwith fluid drug formulation 3932. The final step of the capillary actionfilling process includes extracting the solvent or dispersion medium offluid drug formulation 3932 from within the lumenal space, therebyprecipitating the solute, i.e., therapeutic substance or drug 112,within lumen 103 and creating a drug-filled stent 100. Moreparticularly, stents 100 are retracted into upper chamber 3922, which isstill at or near vapor-liquid equilibrium of solvent 3933, and valve3926 is closed such that the chambers 3922, 3924 are no longer in fluidcommunication. Valve 3926 is closed to isolate fluid drug formulation3932 from the upper chamber 3922 so that evaporation does not occur fromthe fluid drug formulation and additional batches of stents may befilled with the same fluid drug formulation without concentrationchanges. Upper chamber 3922 is then vented to reduce its solvent vaporpressure back to ambient pressure. As the solvent vapor pressure isreduced in the upper chamber, evaporation within lumen 103 of hollowwire 102 is initiated and the solvent of drug fluid formulation 3932 isremoved, thereby precipitating its constituents.

When stents 100 directly contact the fluid drug formulation without awicking means, an additional cleaning step may be utilized after thestent is filled via capillary action in order to remove excess fluiddrug formulation from the exterior surfaces of stents 100. If included,the additional cleaning step is preferably performed after the fillingstep but prior to the solvent evaporation step. Thus, stent 100 mayremain in second chamber 3924 of apparatus 3900 during the cleaning stepor may be retracted into the upper chamber 3922 of apparatus 3900 duringthe cleaning step as shown in FIG. 39. A cleaning element 3995 thatremoves excess fluid drug formulation from the exterior surfaces ofhollow wire 102 of stent 100 may be included within first or secondchamber 3922, 3924 of apparatus 3900. For example, in one embodiment,cleaning element 3995 is a dry sponge (independent from a sponge thatmay be utilized as a wicking means) that stents 100 may be dabbed orblotted on to remove excess fluid drug formulation from the exteriorsurfaces of stent 100. In another embodiment, cleaning element 3995 is areservoir of dry glass beads (independent from any beads being utilizedas a wicking means) that stents 100 may be inserted into to removeexcess fluid drug formulation from the exterior surfaces of hollow wire102 of stent 100. The dry glass beads may be vibrated, i.e., via apiezoelectric crystal, to assist in the cleaning step. In yet anotherembodiment, cleaning element 3995 is a squeegee that stents 100 may beinserted into to remove excess fluid drug formulation from the exteriorsurfaces of stent 100. In yet another embodiment, cleaning element 3995generates movement in order to remove excess fluid drug formulation fromthe exterior surfaces of stents 100. For example, cleaning element 3995may generate force by acceleration and/or deceleration to remove excessfluid drug formulation from the exterior surfaces of hollow wire 102 ofstent 100. More particularly, stents 100 may be accelerated to spin offexcess fluid drug formulation from the exterior surfaces of stents 100.Alternatively or in addition, cleaning element 3995 may be apiezoelectric crystal that generates movement/vibration to removesexcess fluid drug formulation from the exterior surfaces of stent 100. Apiezoelectric crystal may be incorporated onto the carousel/mandrel ofthe stent suspension means in the upper chamber of the apparatus.

In addition or as an alternative to a cleaning step, at least a portionof the exterior surface of hollow wire 102 of stent 100 may be maskedduring the filling procedure to prevent the submersed exterior surfacefrom being exposed to the fluid drug formulation. In one embodiment, amonolayer or coating may be applied over at least a portion of stent 100to mask or cover the exterior surfaces of hollow wire 102 of stent 100that are to be exposed to a fluid drug formulation, while leaving thedrug delivery side ports or openings 104 of stent 100 open so that thefluid drug formulation can fill the lumen of the hollow wire. Themonolayer or coating having any excess fluid drug formulation adheredthereto may be removed after the filling process is complete. In anembodiment in which the fluid drug formulation is hydrophilic, thecoating is preferably hydrophobic. As the lumenal space of the wirefills, the hydrophilic fluid drug formulation does not stick to thecoating or any exposed exterior surfaces of the hollow wire of the stentdue to the hydrophobic property of the coating. In another embodiment,as opposed to a coating, a sleeve that slides over hollow wire 102 maybe utilized to mask or cover the exterior surfaces of hollow wire 102 ofstent 100 that are to be exposed to a fluid drug formulation.

Although the cleaning and/or masking embodiments described above havebeen discussed in conjunction with embodiments in which stents directlycontacts a fluid drug formulation without a wicking means, such cleaningand/or masking embodiments described herein may be utilized with anyembodiment described herein, including those which utilize a wickingmeans. In addition, although the cleaning embodiments described aboveoccur between the filling and drying/evaporation steps of the process,additional and/or alternative cleaning steps may be applied after thedrying/evaporation step of the process. For example, U.S. PatentApplication Publication 2012/0070562 entitled “Apparatus and Methods forFilling a Drug Eluting Medical Device” to Avelar et al., hereinincorporated by reference in its entirety, describes several stentcleaning methods that may be utilized herewith. Any combination of theaforementioned cleaning methods can be employed to clean the stent. Theselection of cleaning method(s) may be governed by factors such as thedrug formulation components and the degree of drug residue after thefilling process via capillary action is complete.

Other Applications of Capillary Filling Process

In addition to filling stents formed via a hollow wire for drugdelivery, embodiments of the capillary action filling process describedabove may be applied to other structures. For example, structures havinga lumen of a sufficiently small size, such as lumen 103 of hollow wire102 of stent 100, can be impregnated with any fluid formulation using acapillary action filling process described above. Since only one sideopening 104 of the stent is required to be exposed to the fluidformulation, fill weight variation and waste is reduced. In addition tostructures having a sufficiently small lumen, structures formed from aporous material, or having a porous material on at least an exteriorsurface thereof, may be impregnated with any fluid formulation using acapillary action filling process described above. For example, animplantable polyurethane sponge may be impregnated with a fluid drugformulation similar to those described herein for in situ delivery.Other examples include impregnating a wound dressing with antibiotic,impregnating a porous bioabsorbable disc that will be implantedsubcutaneously with a fluid drug formulation that suppresses appetite,impregnating a porous bioabsorbable sphere that is to be implanted intoa muscle with a fluid drug formulation that encourages muscle growthafter atrophy, and impregnating a bioabsorbable stent formed from aporous material with a fluid drug formulation similar to those describedherein. Various deformable porous materials that may be impregnated withany fluid formulation using a capillary action filling process describedabove include porous polymers and hydrogels such as polyurethanes, PEG,PLGA, PLA, PGA, and PE, cotton, silk, TELFA, and cellulose.

Rigid materials, such as metals, ceramics, and rigid polymers, are oftenutilized as implants and it may be desired to impregnate a rigidmaterial with a fluid drug formulation. Exemplary rigid materialsinclude aluminum, stainless steel, silver, gold, molybdenum, tungsten,tantalum, bronze, ceramics such as borosilicate, hydroxyapatitie,silicon nitride, zirconium dioxide, and polymers such as PET,Polypropylene, HDPE, PVC, polyamides, and fluoropolymers. In order tobecome porous, rigid materials may undergo processing steps, such as dryetch, a wet or acid etch, application of sintered metal or ceramicpowder, application of a metal mesh, or injection of inert gas duringliquid metal or polymer solidification. After becoming porous, the rigidmaterials may then be impregnated with any fluid formulation using acapillary action filling process described above. For example, a hipimplant formed from a rigid porous material may be impregnated with asteroid to reduce inflammation after implantation or a spinalscrew/plate/rod may be impregnated with an API that encourages bonegrowth and/or healing.

While various embodiments of the present invention have been describedabove, it should be understood that they have been presented by way ofillustration and example only, and not limitation. It will be apparentto persons skilled in the relevant art that various changes in form anddetail can be made therein without departing from the spirit and scopeof the invention. Thus, the breadth and scope of the present inventionshould not be limited by any of the above-described exemplaryembodiments. It will also be understood that each feature of eachembodiment discussed herein, and of each reference cited herein, can beused in combination with the features of any other embodiment.Furthermore, there is no intention to be bound by any expressed orimplied theory presented in the preceding technical field, background,brief summary or the detailed description. All patents and publicationsdiscussed herein are incorporated by reference herein in their entirety.

What is claimed is:
 1. A method of filling a fluid drug formulationwithin a lumenal space of a hollow wire having a plurality of sideopenings along a length thereof that forms a medical device, the methodcomprising the steps of: placing the medical device formed from a hollowwire having a plurality of side openings within a chamber that houses afluid drug formulation and a means for wicking that is in contact withthe fluid drug formulation, wherein the chamber is at or near thevapor-liquid equilibrium of a solvent of the fluid drug formulation;placing a portion of the medical device into contact with the means forwicking such that at least one of the plurality of side openings is incontact with the means for wicking; and maintaining contact between themeans for wicking and the selected portion of the medical device until alumenal space defined by the hollow wire is filled with the fluid drugformulation via capillary action through the at least one of theplurality of side openings in contact with the means for wicking,wherein the means for wicking is a plurality of beads.
 2. The method ofclaim 1, further comprising the steps of: retracting the medical devicesuch that the portion of the medical device is no longer in contact withthe means for wicking; and reducing a solvent vapor pressure in thechamber to evaporate a solvent of the fluid drug formulation.
 3. Themethod of claim 2, wherein the step of retracting the medical devicesuch that the portion of the medical device is no longer in contact withthe means for wicking removes excess fluid drug formulation from anexterior surface of the hollow wire during the step of retracting themedical device.
 4. The method of claim 2, wherein the step of reducingthe solvent vapor pressure in the chamber includes venting the chamberback to ambient pressure.
 5. A method of filling a fluid drugformulation within a lumenal space of a hollow wire having a pluralityof side openings along a length thereof openings that forms a medicaldevice, the method comprising the steps of: placing the medical deviceformed from a hollow wire having a plurality of side openings within afirst chamber of an apparatus, wherein the apparatus includes a valvepositioned between the first chamber and a second chamber that houses ameans for wicking that is in contact with a fluid drug formulation andthe valve is closed such that the first chamber and second chamber arenot in fluid communication; opening the valve such that the firstchamber and second chamber are in fluid communication; allowing thefirst and second chambers to reach solvent vapor saturation or nearsolvent vapor saturation; placing a portion of the medical device intocontact with the means for wicking within the second chamber such thatat least one of the plurality of side openings is in contact with themeans for wicking; maintaining contact between the means for wicking andthe selected portion of the medical device until a lumenal space definedby the hollow wire is filled with the fluid drug formulation viacapillary action through the at least one of the plurality of sideopenings in contact with the means for wicking; retracting the medicaldevice such that the portion of the medical device is no longer incontact with the means for wicking and is located within the firstchamber; closing the valve such that the first chamber and secondchamber are not in fluid communication; and reducing a solvent vaporpressure in the first chamber to evaporate a solvent of the fluid drugformulation.
 6. The method of claim 5, wherein the step of allowing thefirst and second chambers to reach solvent vapor saturation includesatomizing droplets within the first and second chambers with anultrasonic spray nozzle.
 7. The method of claim 5, wherein the step ofallowing the first and second chambers to reach solvent vapor saturationincludes increasing a temperature of the solvent.
 8. The method of claim5, wherein the step of allowing the first and second chambers to reachsolvent vapor saturation includes utilizing a fan to create convectionacross a reservoir filled within the solvent of the fluid drugformulation located within the first chamber.
 9. The method of claim 5,further comprising the step of: allowing the first chamber to reachsolvent vapor saturation or near solvent vapor saturation with the valveclosed such that the first chamber and second chamber are not in fluidcommunication, wherein the first chamber houses a reservoir filled withthe solvent of the fluid drug formulation and the step of allowing thefirst chamber to reach solvent vapor saturation is performed after thestep of placing the medical device in the first chamber and prior to thestep of opening the valve.
 10. The method of claim 5, wherein the stepof retracting the medical device such that the portion of the medicaldevice is no longer in contact with the means for wicking removes excessfluid drug formulation from an exterior surface of the hollow wireduring the step of retracting the medical device.
 11. The method ofclaim 10, wherein the means for wicking is an open-celled sponge orfoam.
 12. The method of claim 10, wherein the means for wicking is aplurality of beads.
 13. The method of claim 5, wherein the step ofreducing the solvent vapor pressure in the first chamber includesventing the first chamber back to ambient pressure.